Richard Mark Kirkner

The Infectious Disease Society of America has released new guidelines on the use and reuse of personal protective equipment, most of which address the use of face protection, for health care workers caring for COVID-19 patients. In releasing the guidelines, the IDSA expert guideline panel acknowledged gaps in evidence to support the recommendations, which is why they will be updated regularly as new evidence emerges.

“Our real goal here is to update these guidelines as a live document,” panel chair John Lynch III, MD, MPH, of the University of Washington, Seattle, said in a press briefing. “Looking at whatever research is coming out where it gets to the point where we find that the evidence is strong enough to make a change, I think we’ll need to readdress these recommendations.”

The panel tailored recommendations to the availability of supplies: conventional capacity for usual supplies; contingency capacity, when supplies are conserved, adapted and substituted with occasional reuse of select supplies; and crisis capacity, when critical supplies are lacking.

The guidelines contain the following eight recommendations for encounters with suspected or confirmed COVID-19 patients:

1) Either a surgical mask or N95 (or N99 or PAPR [powered & supplied air respiratory protection]) respirator for routine patient care in a conventional setting.

2) Either a surgical mask or reprocessed respirator as opposed to no mask for routine care in a contingency or crisis setting.

3) No recommendation on the use of double gloves vs. single gloves.

4) No recommendation on the use of shoe covers for any setting.

5) An N95 (or N99 or PAPR) respirator for aerosol-generating procedures in a conventional setting.

6) A reprocessed N95 respirator as opposed to a surgical mask for aerosol-generating procedures in a contingency or crisis setting.

7) Adding a face shield or surgical mask as a cover for an N95 respirator to allow for extended use during respirator shortages when performing aerosol-generating procedures in a contingency or crisis setting. This recommendation carries a caveat: It assumes correct doffing sequence and hand hygiene before and after taking off the face shield or surgical mask cover.

8) In the same scenario, adding a face shield or surgical mask over the N95 respirator so it can be reused, again assuming the correct sequence for hand hygiene.

The guideline was developed using the GRADE approach – for Grading of Recommendations Assessment, Development, and Evaluation – and a modified methodology for developing rapid recommendations. The levels of evidence supporting each recommendation vary from moderate for the first two to knowledge gap for the third and fourth to very low certainty for the last four.

“You can see that the eight recommendations that were made, a large part of them are really focused on masks, but there are a huge number of other disparate questions that need to be answered where there is really no good evidence basis,” Dr. Lynch said. “If we see any new evidence around that, we can at least provide commentary but I would really hope evidence-based recommendations around some of those interventions.”

Panel member Allison McGeer, MD, FRCPC, of the University of Toronto, explained the lack of evidence supporting infection prevention in hospitals. “In medicine we tend to look at individual patterns and individual patient outcomes,” she said. “When you’re looking at infection prevention, you’re looking at health systems and their outcomes, and it’s much harder to randomize hospitals or a state or a country to one particular policy about how to protect patients from infections in hospitals.”

SOURCE: Lynch JB et al. IDSA. April 27, 2020.

The Infectious Disease Society of America has released new guidelines on the use and reuse of personal protective equipment, most of which address the use of face protection, for health care workers caring for COVID-19 patients. In releasing the guidelines, the IDSA expert guideline panel acknowledged gaps in evidence to support the recommendations, which is why they will be updated regularly as new evidence emerges.

“Our real goal here is to update these guidelines as a live document,” panel chair John Lynch III, MD, MPH, of the University of Washington, Seattle, said in a press briefing. “Looking at whatever research is coming out where it gets to the point where we find that the evidence is strong enough to make a change, I think we’ll need to readdress these recommendations.”

The panel tailored recommendations to the availability of supplies: conventional capacity for usual supplies; contingency capacity, when supplies are conserved, adapted and substituted with occasional reuse of select supplies; and crisis capacity, when critical supplies are lacking.

The guidelines contain the following eight recommendations for encounters with suspected or confirmed COVID-19 patients:

1) Either a surgical mask or N95 (or N99 or PAPR [powered & supplied air respiratory protection]) respirator for routine patient care in a conventional setting.

2) Either a surgical mask or reprocessed respirator as opposed to no mask for routine care in a contingency or crisis setting.

3) No recommendation on the use of double gloves vs. single gloves.

4) No recommendation on the use of shoe covers for any setting.

5) An N95 (or N99 or PAPR) respirator for aerosol-generating procedures in a conventional setting.

6) A reprocessed N95 respirator as opposed to a surgical mask for aerosol-generating procedures in a contingency or crisis setting.

7) Adding a face shield or surgical mask as a cover for an N95 respirator to allow for extended use during respirator shortages when performing aerosol-generating procedures in a contingency or crisis setting. This recommendation carries a caveat: It assumes correct doffing sequence and hand hygiene before and after taking off the face shield or surgical mask cover.

8) In the same scenario, adding a face shield or surgical mask over the N95 respirator so it can be reused, again assuming the correct sequence for hand hygiene.

The guideline was developed using the GRADE approach – for Grading of Recommendations Assessment, Development, and Evaluation – and a modified methodology for developing rapid recommendations. The levels of evidence supporting each recommendation vary from moderate for the first two to knowledge gap for the third and fourth to very low certainty for the last four.

“You can see that the eight recommendations that were made, a large part of them are really focused on masks, but there are a huge number of other disparate questions that need to be answered where there is really no good evidence basis,” Dr. Lynch said. “If we see any new evidence around that, we can at least provide commentary but I would really hope evidence-based recommendations around some of those interventions.”

Panel member Allison McGeer, MD, FRCPC, of the University of Toronto, explained the lack of evidence supporting infection prevention in hospitals. “In medicine we tend to look at individual patterns and individual patient outcomes,” she said. “When you’re looking at infection prevention, you’re looking at health systems and their outcomes, and it’s much harder to randomize hospitals or a state or a country to one particular policy about how to protect patients from infections in hospitals.”

SOURCE: Lynch JB et al. IDSA. April 27, 2020.

The Infectious Disease Society of America has released new guidelines on the use and reuse of personal protective equipment, most of which address the use of face protection, for health care workers caring for COVID-19 patients. In releasing the guidelines, the IDSA expert guideline panel acknowledged gaps in evidence to support the recommendations, which is why they will be updated regularly as new evidence emerges.

“Our real goal here is to update these guidelines as a live document,” panel chair John Lynch III, MD, MPH, of the University of Washington, Seattle, said in a press briefing. “Looking at whatever research is coming out where it gets to the point where we find that the evidence is strong enough to make a change, I think we’ll need to readdress these recommendations.”

The panel tailored recommendations to the availability of supplies: conventional capacity for usual supplies; contingency capacity, when supplies are conserved, adapted and substituted with occasional reuse of select supplies; and crisis capacity, when critical supplies are lacking.

The guidelines contain the following eight recommendations for encounters with suspected or confirmed COVID-19 patients:

1) Either a surgical mask or N95 (or N99 or PAPR [powered & supplied air respiratory protection]) respirator for routine patient care in a conventional setting.

2) Either a surgical mask or reprocessed respirator as opposed to no mask for routine care in a contingency or crisis setting.

3) No recommendation on the use of double gloves vs. single gloves.

4) No recommendation on the use of shoe covers for any setting.

5) An N95 (or N99 or PAPR) respirator for aerosol-generating procedures in a conventional setting.

6) A reprocessed N95 respirator as opposed to a surgical mask for aerosol-generating procedures in a contingency or crisis setting.

7) Adding a face shield or surgical mask as a cover for an N95 respirator to allow for extended use during respirator shortages when performing aerosol-generating procedures in a contingency or crisis setting. This recommendation carries a caveat: It assumes correct doffing sequence and hand hygiene before and after taking off the face shield or surgical mask cover.

8) In the same scenario, adding a face shield or surgical mask over the N95 respirator so it can be reused, again assuming the correct sequence for hand hygiene.

The guideline was developed using the GRADE approach – for Grading of Recommendations Assessment, Development, and Evaluation – and a modified methodology for developing rapid recommendations. The levels of evidence supporting each recommendation vary from moderate for the first two to knowledge gap for the third and fourth to very low certainty for the last four.

“You can see that the eight recommendations that were made, a large part of them are really focused on masks, but there are a huge number of other disparate questions that need to be answered where there is really no good evidence basis,” Dr. Lynch said. “If we see any new evidence around that, we can at least provide commentary but I would really hope evidence-based recommendations around some of those interventions.”

Panel member Allison McGeer, MD, FRCPC, of the University of Toronto, explained the lack of evidence supporting infection prevention in hospitals. “In medicine we tend to look at individual patterns and individual patient outcomes,” she said. “When you’re looking at infection prevention, you’re looking at health systems and their outcomes, and it’s much harder to randomize hospitals or a state or a country to one particular policy about how to protect patients from infections in hospitals.”

SOURCE: Lynch JB et al. IDSA. April 27, 2020.

A far-reaching surveillance initiative was implemented in Shenzhen, China, to isolate and contact trace people suspected of having the COVID-19 coronavirus. This initiative led to faster confirmation of new cases and reduced the window of time during which people were infectious in the community. This potentially reduced the number of new infections that arose from each case, according to a study of patients and contacts over 4 weeks (Lancet Infect Dis. 2020 Apr 27. doi: 10.1016/S1473-3099[20]30287-5).

CDC/John Hierholzer, MD

“The experience of COVID-19 in the city of Shenzhen may demonstrate the huge scale of testing and contact tracing that’s needed to reduce the virus spreading,” said study coauthor Ting Ma, PhD, of Harbin Institute of Technology at Shenzhen.

Dr. Ma acknowledged that some of the measures the program used, such as isolating people outside their homes, may be difficult to impose in other countries, “but we urge governments to consider our findings in the global response to COVID-19.”

The study followed 391 coronavirus cases and 1,286 close contacts identified by the Shenzhen Center for Disease Control and Prevention from Jan. 14 to Feb. 12 this year. The study showed that contact tracing led to confirming new diagnoses within 3.2 days on average vs. 5.5 for symptom-based surveillance, and reduced the time it took to isolate newly infected people by 2 days, from an average of 4.6 to 2.7 days. Eighty-seven people were diagnosed with COVID-19 after they were contact traced and tested. Twenty percent of them had no symptoms, and 29% had no fever. Three deaths occurred in the group during the study period.

The surveillance program was comprehensive and intense. On Jan. 8, the Shenzhen CDC started monitoring travelers from Hubei province, of which Wuhan is the capital, for symptoms of COVID-19. Shenzhen is a city of about 12.5 million people in southeastern China, near Hong Kong, and is about 560 miles south of Wuhan. Over the next 2 weeks, the Shenzhen CDC expanded that surveillance program to all travelers from Hubei regardless of symptoms, along with local hospital patients and people detected by fever screenings at area clinics.

Suspected cases and close contacts underwent nasal-swab testing at 40 different locations in the city. The program identified close contacts through contact tracing, and included anyone who lived in the same dwelling, shared a meal, traveled, or had a social interaction with an index 2 days before symptoms appeared. Casual contacts and some close contacts, such as clinic nurses, who wore masks during the encounters were excluded.

“To achieve similar results, other countries might be able to combine near-universal testing and intensive contact tracing with social distancing and partial lockdowns,” said Dr. Ma. “Although no lockdown measures were introduced in Shenzhen until the end of our study period, Wuhan’s lockdown could have significantly restricted the spread of coronavirus to Shenzhen.”

The researchers noted that children are as susceptible to the virus as are adults, even though their symptoms are not as severe as those of adults. The rate of infection in children 10 and younger was similar to the overall infection rate, 7.4% vs. 6.6%, so the researchers noted that surveillance measures should target them as well.

“This study to me confirms a lot of what we’ve already known,” Aaron E. Glatt, MD, chairman of medicine and an epidemiologist at Mount Sinai South Nassau in Oceanside, N.Y., said in an interview. “It’s an elegant study, but at the same time it sends us a message that we’re at a critical point of time for us to intervene and prevent cases at the very beginning.”

He acknowledged that the Shenzhen effort was intense. “It’s always a resource-intense requirement to do such extensive contact tracing, but that doesn’t mean it shouldn’t be done to the best of your ability to do so,” he said. He was struck by the low relative rate of infection among contacts in the study – around 7%. “There are differences obviously in infection rates in every outbreak,” he said. “Every individual has their own particular infection rate. While we can take ranges and statistical guesses for every individual patient, it could be very high or very low, and that’s most critical to nip it in the bud.”

Lead author Qifang Bi and study coauthors had no financial relationships to disclose.

SOURCE: Bi Q et al. Lancet Infect Dis. 2020 Apr 27. doi: 10.1016/S1473-3099(20)30287-5.

A far-reaching surveillance initiative was implemented in Shenzhen, China, to isolate and contact trace people suspected of having the COVID-19 coronavirus. This initiative led to faster confirmation of new cases and reduced the window of time during which people were infectious in the community. This potentially reduced the number of new infections that arose from each case, according to a study of patients and contacts over 4 weeks (Lancet Infect Dis. 2020 Apr 27. doi: 10.1016/S1473-3099[20]30287-5).

CDC/John Hierholzer, MD

“The experience of COVID-19 in the city of Shenzhen may demonstrate the huge scale of testing and contact tracing that’s needed to reduce the virus spreading,” said study coauthor Ting Ma, PhD, of Harbin Institute of Technology at Shenzhen.

Dr. Ma acknowledged that some of the measures the program used, such as isolating people outside their homes, may be difficult to impose in other countries, “but we urge governments to consider our findings in the global response to COVID-19.”

The study followed 391 coronavirus cases and 1,286 close contacts identified by the Shenzhen Center for Disease Control and Prevention from Jan. 14 to Feb. 12 this year. The study showed that contact tracing led to confirming new diagnoses within 3.2 days on average vs. 5.5 for symptom-based surveillance, and reduced the time it took to isolate newly infected people by 2 days, from an average of 4.6 to 2.7 days. Eighty-seven people were diagnosed with COVID-19 after they were contact traced and tested. Twenty percent of them had no symptoms, and 29% had no fever. Three deaths occurred in the group during the study period.

The surveillance program was comprehensive and intense. On Jan. 8, the Shenzhen CDC started monitoring travelers from Hubei province, of which Wuhan is the capital, for symptoms of COVID-19. Shenzhen is a city of about 12.5 million people in southeastern China, near Hong Kong, and is about 560 miles south of Wuhan. Over the next 2 weeks, the Shenzhen CDC expanded that surveillance program to all travelers from Hubei regardless of symptoms, along with local hospital patients and people detected by fever screenings at area clinics.

Suspected cases and close contacts underwent nasal-swab testing at 40 different locations in the city. The program identified close contacts through contact tracing, and included anyone who lived in the same dwelling, shared a meal, traveled, or had a social interaction with an index 2 days before symptoms appeared. Casual contacts and some close contacts, such as clinic nurses, who wore masks during the encounters were excluded.

“To achieve similar results, other countries might be able to combine near-universal testing and intensive contact tracing with social distancing and partial lockdowns,” said Dr. Ma. “Although no lockdown measures were introduced in Shenzhen until the end of our study period, Wuhan’s lockdown could have significantly restricted the spread of coronavirus to Shenzhen.”

The researchers noted that children are as susceptible to the virus as are adults, even though their symptoms are not as severe as those of adults. The rate of infection in children 10 and younger was similar to the overall infection rate, 7.4% vs. 6.6%, so the researchers noted that surveillance measures should target them as well.

“This study to me confirms a lot of what we’ve already known,” Aaron E. Glatt, MD, chairman of medicine and an epidemiologist at Mount Sinai South Nassau in Oceanside, N.Y., said in an interview. “It’s an elegant study, but at the same time it sends us a message that we’re at a critical point of time for us to intervene and prevent cases at the very beginning.”

He acknowledged that the Shenzhen effort was intense. “It’s always a resource-intense requirement to do such extensive contact tracing, but that doesn’t mean it shouldn’t be done to the best of your ability to do so,” he said. He was struck by the low relative rate of infection among contacts in the study – around 7%. “There are differences obviously in infection rates in every outbreak,” he said. “Every individual has their own particular infection rate. While we can take ranges and statistical guesses for every individual patient, it could be very high or very low, and that’s most critical to nip it in the bud.”

Lead author Qifang Bi and study coauthors had no financial relationships to disclose.

SOURCE: Bi Q et al. Lancet Infect Dis. 2020 Apr 27. doi: 10.1016/S1473-3099(20)30287-5.

A far-reaching surveillance initiative was implemented in Shenzhen, China, to isolate and contact trace people suspected of having the COVID-19 coronavirus. This initiative led to faster confirmation of new cases and reduced the window of time during which people were infectious in the community. This potentially reduced the number of new infections that arose from each case, according to a study of patients and contacts over 4 weeks (Lancet Infect Dis. 2020 Apr 27. doi: 10.1016/S1473-3099[20]30287-5).

CDC/John Hierholzer, MD

“The experience of COVID-19 in the city of Shenzhen may demonstrate the huge scale of testing and contact tracing that’s needed to reduce the virus spreading,” said study coauthor Ting Ma, PhD, of Harbin Institute of Technology at Shenzhen.

Dr. Ma acknowledged that some of the measures the program used, such as isolating people outside their homes, may be difficult to impose in other countries, “but we urge governments to consider our findings in the global response to COVID-19.”

The study followed 391 coronavirus cases and 1,286 close contacts identified by the Shenzhen Center for Disease Control and Prevention from Jan. 14 to Feb. 12 this year. The study showed that contact tracing led to confirming new diagnoses within 3.2 days on average vs. 5.5 for symptom-based surveillance, and reduced the time it took to isolate newly infected people by 2 days, from an average of 4.6 to 2.7 days. Eighty-seven people were diagnosed with COVID-19 after they were contact traced and tested. Twenty percent of them had no symptoms, and 29% had no fever. Three deaths occurred in the group during the study period.

The surveillance program was comprehensive and intense. On Jan. 8, the Shenzhen CDC started monitoring travelers from Hubei province, of which Wuhan is the capital, for symptoms of COVID-19. Shenzhen is a city of about 12.5 million people in southeastern China, near Hong Kong, and is about 560 miles south of Wuhan. Over the next 2 weeks, the Shenzhen CDC expanded that surveillance program to all travelers from Hubei regardless of symptoms, along with local hospital patients and people detected by fever screenings at area clinics.

Suspected cases and close contacts underwent nasal-swab testing at 40 different locations in the city. The program identified close contacts through contact tracing, and included anyone who lived in the same dwelling, shared a meal, traveled, or had a social interaction with an index 2 days before symptoms appeared. Casual contacts and some close contacts, such as clinic nurses, who wore masks during the encounters were excluded.

“To achieve similar results, other countries might be able to combine near-universal testing and intensive contact tracing with social distancing and partial lockdowns,” said Dr. Ma. “Although no lockdown measures were introduced in Shenzhen until the end of our study period, Wuhan’s lockdown could have significantly restricted the spread of coronavirus to Shenzhen.”

The researchers noted that children are as susceptible to the virus as are adults, even though their symptoms are not as severe as those of adults. The rate of infection in children 10 and younger was similar to the overall infection rate, 7.4% vs. 6.6%, so the researchers noted that surveillance measures should target them as well.

“This study to me confirms a lot of what we’ve already known,” Aaron E. Glatt, MD, chairman of medicine and an epidemiologist at Mount Sinai South Nassau in Oceanside, N.Y., said in an interview. “It’s an elegant study, but at the same time it sends us a message that we’re at a critical point of time for us to intervene and prevent cases at the very beginning.”

He acknowledged that the Shenzhen effort was intense. “It’s always a resource-intense requirement to do such extensive contact tracing, but that doesn’t mean it shouldn’t be done to the best of your ability to do so,” he said. He was struck by the low relative rate of infection among contacts in the study – around 7%. “There are differences obviously in infection rates in every outbreak,” he said. “Every individual has their own particular infection rate. While we can take ranges and statistical guesses for every individual patient, it could be very high or very low, and that’s most critical to nip it in the bud.”

Lead author Qifang Bi and study coauthors had no financial relationships to disclose.

SOURCE: Bi Q et al. Lancet Infect Dis. 2020 Apr 27. doi: 10.1016/S1473-3099(20)30287-5.

The monoclonal antibody omalizumab, already approved to treat allergic asthma and urticaria, has been shown to improve symptoms of patients who have chronic rhinosinusitis and nasal polyps (CRSwNP), according to recent research released as an abstract from the American Academy of Allergy, Asthma, and Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

“When you give this drug to patients who have nasal polyposis and concomitant asthma, you are effectively treating both the upper and lower airway disease components,” Jonathan Corren, MD, of the University of California, Los Angeles, said in an interview. “Typically, people with nasal polyp disease have worse nasal disease than people without asthma. In addition, asthma is also generally worse in patients with nasal polyposis,” he added.

Dr. Corren reported results of a subset of patients with corticosteroid-refractory CRSwNP and comorbid asthma enrolled in phase III, placebo-controlled, 24-week, trials of omalizumab, POLYP1 (n = 74) and POLYP2 (n = 77). The analysis excluded patients who were on oral steroids or high-dose steroid inhaler therapy so the effectiveness of omalizumab could be evaluated without interfering factors, Dr. Corren explained. As a result, the study population consisted of patients with mild to moderate asthma. Dr. Corren is also principal investigator of the POLYP1 trial.

The analysis compared changes in Asthma Quality of Life Questionnaire (AQLQ) and sino-nasal outcome test (SNOT-22) measures after 24 weeks of treatment with those seen with placebo.

“With regard to asthma outcomes, we found there was a significant increase in the odds ratio that patients who received omalizumab would achieve a minimal, clinically important improvement in their asthma quality of life,” Dr. Corren said .

The study estimated the odds ratio for minimal clinically important difference in AQLQ at 24 weeks was 3.9 (95% confidence interval, 1.5-9.7; P = .0043), which Dr. Corren called “quite significant.” SNOT-22 scores showed a mean improvement of 23.3 from baseline to week 24, compared with a worsening of 8.4 in placebo (P = .0001).

Omalizumab is approved for treatment of perennial allergies and urticaria. Chronic rhinosinusitis with nasal polyps would be a third indication if the Food and Drug Administration approves it, Dr. Corren noted.

Genentech sponsored the subset analysis. Hoffmann-La Roche, Genentech’s parent company, is sponsor of the POLYP1 and POLYP2 trials. Dr. Corren disclosed financial relationships with Genentech.

SOURCE: Corren J et al. AAAAI, Session 4608, Abstract 813.

The monoclonal antibody omalizumab, already approved to treat allergic asthma and urticaria, has been shown to improve symptoms of patients who have chronic rhinosinusitis and nasal polyps (CRSwNP), according to recent research released as an abstract from the American Academy of Allergy, Asthma, and Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

“When you give this drug to patients who have nasal polyposis and concomitant asthma, you are effectively treating both the upper and lower airway disease components,” Jonathan Corren, MD, of the University of California, Los Angeles, said in an interview. “Typically, people with nasal polyp disease have worse nasal disease than people without asthma. In addition, asthma is also generally worse in patients with nasal polyposis,” he added.

Dr. Corren reported results of a subset of patients with corticosteroid-refractory CRSwNP and comorbid asthma enrolled in phase III, placebo-controlled, 24-week, trials of omalizumab, POLYP1 (n = 74) and POLYP2 (n = 77). The analysis excluded patients who were on oral steroids or high-dose steroid inhaler therapy so the effectiveness of omalizumab could be evaluated without interfering factors, Dr. Corren explained. As a result, the study population consisted of patients with mild to moderate asthma. Dr. Corren is also principal investigator of the POLYP1 trial.

The analysis compared changes in Asthma Quality of Life Questionnaire (AQLQ) and sino-nasal outcome test (SNOT-22) measures after 24 weeks of treatment with those seen with placebo.

“With regard to asthma outcomes, we found there was a significant increase in the odds ratio that patients who received omalizumab would achieve a minimal, clinically important improvement in their asthma quality of life,” Dr. Corren said .

The study estimated the odds ratio for minimal clinically important difference in AQLQ at 24 weeks was 3.9 (95% confidence interval, 1.5-9.7; P = .0043), which Dr. Corren called “quite significant.” SNOT-22 scores showed a mean improvement of 23.3 from baseline to week 24, compared with a worsening of 8.4 in placebo (P = .0001).

Omalizumab is approved for treatment of perennial allergies and urticaria. Chronic rhinosinusitis with nasal polyps would be a third indication if the Food and Drug Administration approves it, Dr. Corren noted.

Genentech sponsored the subset analysis. Hoffmann-La Roche, Genentech’s parent company, is sponsor of the POLYP1 and POLYP2 trials. Dr. Corren disclosed financial relationships with Genentech.

SOURCE: Corren J et al. AAAAI, Session 4608, Abstract 813.

The monoclonal antibody omalizumab, already approved to treat allergic asthma and urticaria, has been shown to improve symptoms of patients who have chronic rhinosinusitis and nasal polyps (CRSwNP), according to recent research released as an abstract from the American Academy of Allergy, Asthma, and Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

“When you give this drug to patients who have nasal polyposis and concomitant asthma, you are effectively treating both the upper and lower airway disease components,” Jonathan Corren, MD, of the University of California, Los Angeles, said in an interview. “Typically, people with nasal polyp disease have worse nasal disease than people without asthma. In addition, asthma is also generally worse in patients with nasal polyposis,” he added.

Dr. Corren reported results of a subset of patients with corticosteroid-refractory CRSwNP and comorbid asthma enrolled in phase III, placebo-controlled, 24-week, trials of omalizumab, POLYP1 (n = 74) and POLYP2 (n = 77). The analysis excluded patients who were on oral steroids or high-dose steroid inhaler therapy so the effectiveness of omalizumab could be evaluated without interfering factors, Dr. Corren explained. As a result, the study population consisted of patients with mild to moderate asthma. Dr. Corren is also principal investigator of the POLYP1 trial.

The analysis compared changes in Asthma Quality of Life Questionnaire (AQLQ) and sino-nasal outcome test (SNOT-22) measures after 24 weeks of treatment with those seen with placebo.

“With regard to asthma outcomes, we found there was a significant increase in the odds ratio that patients who received omalizumab would achieve a minimal, clinically important improvement in their asthma quality of life,” Dr. Corren said .

The study estimated the odds ratio for minimal clinically important difference in AQLQ at 24 weeks was 3.9 (95% confidence interval, 1.5-9.7; P = .0043), which Dr. Corren called “quite significant.” SNOT-22 scores showed a mean improvement of 23.3 from baseline to week 24, compared with a worsening of 8.4 in placebo (P = .0001).

Omalizumab is approved for treatment of perennial allergies and urticaria. Chronic rhinosinusitis with nasal polyps would be a third indication if the Food and Drug Administration approves it, Dr. Corren noted.

Genentech sponsored the subset analysis. Hoffmann-La Roche, Genentech’s parent company, is sponsor of the POLYP1 and POLYP2 trials. Dr. Corren disclosed financial relationships with Genentech.

SOURCE: Corren J et al. AAAAI, Session 4608, Abstract 813.

A large pooled analysis of almost 24,000 women showed women who breastfed had a 24% lower risk of invasive ovarian cancer.

Bonnie Becker/MDedge News

Multiple studies have reported a link between breastfeeding and a reduced risk of ovarian cancer, but other studies have found no such link, and the evidence that the protective effects differ by histologic types has been inconclusive.

“This large study with extensive information on breastfeeding provides epidemiological evidence that breastfeeding, a potentially modifiable factor, may confer significant reduction in ovarian cancer risk, including high-grade serous, the deadliest subtype,” Ana Babic, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, and colleagues reported in JAMA Oncology.

Dr. Babic led the study of a pooled analysis of women from 13 case-control studies participating in the Ovarian Cancer Association Consortium. The study evaluated 9,973 women who had ovarian cancer and 13,843 controls, with a mean age of 57 and 56 years, respectively. The data were collected over 20 years through December 2009. Dr. Babic and colleagues claimed that this is the largest study of breastfeeding and ovarian cancer risk to date.

Besides calculating a lower risk of invasive cancer, the analysis also determined that any breastfeeding was associated with a 28% lower risk of borderline cancers, compared with women who never breastfed. “Among invasive tumors, the association was statistically significant for high-grade serous, endometrioid and clear-cell tumors,” Dr. Babic and colleagues wrote, with 25%, 27% and 22% reduced risk, respectively. The researchers also noted a similar, although not statistically significant, reduced risk for low-grade serous tumors, but no such association for mucinous tumors. For borderline tumors, breastfeeding correlated with a 32% lower risk for mucinous tumors and 23% reduction in risk for serous tumors.

The analysis included five studies with data on exclusive breastfeeding. Women who breastfed exclusively for at least 3 months had a 19% reduced risk of ovarian cancer, compared with women who never breastfed, while women who breastfed albeit not exclusively for 3 months had a 30% reduced risk. The analysis also found an association between longer duration of breastfeeding and reduced risk of invasive ovarian cancer: less than 3 months duration per child was associated with an 18% lower risk, while more than 12 months was associated with a 34% lower risk (P < .001). Other factors that seemed to mitigate risk were older age when breastfeeding and breastfeeding within the previous 10 years.

One of the strengths of the studies is that it separated low-grade and the more common and deadly high-grade serous tumors. While the analysis found similar trends with endometrioid ovarian cancers, it didn’t reach a conclusion about other invasive histotypes because there were fewer cases to evaluate. Because the study population was predominantly white, the researchers acknowledged they could not sufficiently evaluate patterns among blacks, Asian, and other ethnic groups. “The association between breastfeeding and ovarian cancer needs to be investigated in large populations of other races and ethnicities,” Dr. Babic and colleagues added.

Nonetheless, they noted that their results support the World Health Organization recommendations of at least 6 months of exclusive breastfeeding and continued breastfeeding with complementary foods for 2 years or more, even though breastfeeding for less than 3 months is associated with a significant reduction in ovarian cancer risk.

The study is significant because of its “thoughtful approach to addressing potential confounders (parity, age, etc.),” said David Barrington, MD, gynecologic oncology fellow at Ohio State University James Cancer Center in Columbus.

“For general obstetricians and gynecologists, this study provides an additional reason to advocate for breastfeeding,” Dr. Barrington added. “This data should be included in a thorough discussion of the multitudes of benefits breastfeeding provides to both the infant and the mother.”

He added that future studies should evaluate breastfeeding and ovarian cancer risks in a more ethnically diverse population. “Understanding the potential impact of modifiable risk factors for ovarian cancer is paramount to overcoming racial disparities in outcomes,” Dr. Barrington said.

The study was supported by the U.S. National Cancer Institute. Dr. Babic reported grants from the U.S. National Institutes of Health. Some coauthors reported grants from the NIH, the National Health and Medical Research Council of Australia, the Federal Ministry of Education and Research of Germany, the Danish Cancer Society, or the Mermaid I Project. Some coauthors had no disclosures to report. Dr. Barrington has no relevant relationships to disclose.

SOURCE: Babic A et al. JAMA Oncology. 2020. doi: 10.1001/jamaoncol.2020.0421.

A large pooled analysis of almost 24,000 women showed women who breastfed had a 24% lower risk of invasive ovarian cancer.

Bonnie Becker/MDedge News

Multiple studies have reported a link between breastfeeding and a reduced risk of ovarian cancer, but other studies have found no such link, and the evidence that the protective effects differ by histologic types has been inconclusive.

“This large study with extensive information on breastfeeding provides epidemiological evidence that breastfeeding, a potentially modifiable factor, may confer significant reduction in ovarian cancer risk, including high-grade serous, the deadliest subtype,” Ana Babic, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, and colleagues reported in JAMA Oncology.

Dr. Babic led the study of a pooled analysis of women from 13 case-control studies participating in the Ovarian Cancer Association Consortium. The study evaluated 9,973 women who had ovarian cancer and 13,843 controls, with a mean age of 57 and 56 years, respectively. The data were collected over 20 years through December 2009. Dr. Babic and colleagues claimed that this is the largest study of breastfeeding and ovarian cancer risk to date.

Besides calculating a lower risk of invasive cancer, the analysis also determined that any breastfeeding was associated with a 28% lower risk of borderline cancers, compared with women who never breastfed. “Among invasive tumors, the association was statistically significant for high-grade serous, endometrioid and clear-cell tumors,” Dr. Babic and colleagues wrote, with 25%, 27% and 22% reduced risk, respectively. The researchers also noted a similar, although not statistically significant, reduced risk for low-grade serous tumors, but no such association for mucinous tumors. For borderline tumors, breastfeeding correlated with a 32% lower risk for mucinous tumors and 23% reduction in risk for serous tumors.

The analysis included five studies with data on exclusive breastfeeding. Women who breastfed exclusively for at least 3 months had a 19% reduced risk of ovarian cancer, compared with women who never breastfed, while women who breastfed albeit not exclusively for 3 months had a 30% reduced risk. The analysis also found an association between longer duration of breastfeeding and reduced risk of invasive ovarian cancer: less than 3 months duration per child was associated with an 18% lower risk, while more than 12 months was associated with a 34% lower risk (P < .001). Other factors that seemed to mitigate risk were older age when breastfeeding and breastfeeding within the previous 10 years.

One of the strengths of the studies is that it separated low-grade and the more common and deadly high-grade serous tumors. While the analysis found similar trends with endometrioid ovarian cancers, it didn’t reach a conclusion about other invasive histotypes because there were fewer cases to evaluate. Because the study population was predominantly white, the researchers acknowledged they could not sufficiently evaluate patterns among blacks, Asian, and other ethnic groups. “The association between breastfeeding and ovarian cancer needs to be investigated in large populations of other races and ethnicities,” Dr. Babic and colleagues added.

Nonetheless, they noted that their results support the World Health Organization recommendations of at least 6 months of exclusive breastfeeding and continued breastfeeding with complementary foods for 2 years or more, even though breastfeeding for less than 3 months is associated with a significant reduction in ovarian cancer risk.

The study is significant because of its “thoughtful approach to addressing potential confounders (parity, age, etc.),” said David Barrington, MD, gynecologic oncology fellow at Ohio State University James Cancer Center in Columbus.

“For general obstetricians and gynecologists, this study provides an additional reason to advocate for breastfeeding,” Dr. Barrington added. “This data should be included in a thorough discussion of the multitudes of benefits breastfeeding provides to both the infant and the mother.”

He added that future studies should evaluate breastfeeding and ovarian cancer risks in a more ethnically diverse population. “Understanding the potential impact of modifiable risk factors for ovarian cancer is paramount to overcoming racial disparities in outcomes,” Dr. Barrington said.

The study was supported by the U.S. National Cancer Institute. Dr. Babic reported grants from the U.S. National Institutes of Health. Some coauthors reported grants from the NIH, the National Health and Medical Research Council of Australia, the Federal Ministry of Education and Research of Germany, the Danish Cancer Society, or the Mermaid I Project. Some coauthors had no disclosures to report. Dr. Barrington has no relevant relationships to disclose.

SOURCE: Babic A et al. JAMA Oncology. 2020. doi: 10.1001/jamaoncol.2020.0421.

A large pooled analysis of almost 24,000 women showed women who breastfed had a 24% lower risk of invasive ovarian cancer.

Bonnie Becker/MDedge News

Multiple studies have reported a link between breastfeeding and a reduced risk of ovarian cancer, but other studies have found no such link, and the evidence that the protective effects differ by histologic types has been inconclusive.

“This large study with extensive information on breastfeeding provides epidemiological evidence that breastfeeding, a potentially modifiable factor, may confer significant reduction in ovarian cancer risk, including high-grade serous, the deadliest subtype,” Ana Babic, PhD, of Dana-Farber Cancer Institute and Harvard Medical School, both in Boston, and colleagues reported in JAMA Oncology.

Dr. Babic led the study of a pooled analysis of women from 13 case-control studies participating in the Ovarian Cancer Association Consortium. The study evaluated 9,973 women who had ovarian cancer and 13,843 controls, with a mean age of 57 and 56 years, respectively. The data were collected over 20 years through December 2009. Dr. Babic and colleagues claimed that this is the largest study of breastfeeding and ovarian cancer risk to date.

Besides calculating a lower risk of invasive cancer, the analysis also determined that any breastfeeding was associated with a 28% lower risk of borderline cancers, compared with women who never breastfed. “Among invasive tumors, the association was statistically significant for high-grade serous, endometrioid and clear-cell tumors,” Dr. Babic and colleagues wrote, with 25%, 27% and 22% reduced risk, respectively. The researchers also noted a similar, although not statistically significant, reduced risk for low-grade serous tumors, but no such association for mucinous tumors. For borderline tumors, breastfeeding correlated with a 32% lower risk for mucinous tumors and 23% reduction in risk for serous tumors.

The analysis included five studies with data on exclusive breastfeeding. Women who breastfed exclusively for at least 3 months had a 19% reduced risk of ovarian cancer, compared with women who never breastfed, while women who breastfed albeit not exclusively for 3 months had a 30% reduced risk. The analysis also found an association between longer duration of breastfeeding and reduced risk of invasive ovarian cancer: less than 3 months duration per child was associated with an 18% lower risk, while more than 12 months was associated with a 34% lower risk (P < .001). Other factors that seemed to mitigate risk were older age when breastfeeding and breastfeeding within the previous 10 years.

One of the strengths of the studies is that it separated low-grade and the more common and deadly high-grade serous tumors. While the analysis found similar trends with endometrioid ovarian cancers, it didn’t reach a conclusion about other invasive histotypes because there were fewer cases to evaluate. Because the study population was predominantly white, the researchers acknowledged they could not sufficiently evaluate patterns among blacks, Asian, and other ethnic groups. “The association between breastfeeding and ovarian cancer needs to be investigated in large populations of other races and ethnicities,” Dr. Babic and colleagues added.

Nonetheless, they noted that their results support the World Health Organization recommendations of at least 6 months of exclusive breastfeeding and continued breastfeeding with complementary foods for 2 years or more, even though breastfeeding for less than 3 months is associated with a significant reduction in ovarian cancer risk.

The study is significant because of its “thoughtful approach to addressing potential confounders (parity, age, etc.),” said David Barrington, MD, gynecologic oncology fellow at Ohio State University James Cancer Center in Columbus.

“For general obstetricians and gynecologists, this study provides an additional reason to advocate for breastfeeding,” Dr. Barrington added. “This data should be included in a thorough discussion of the multitudes of benefits breastfeeding provides to both the infant and the mother.”

He added that future studies should evaluate breastfeeding and ovarian cancer risks in a more ethnically diverse population. “Understanding the potential impact of modifiable risk factors for ovarian cancer is paramount to overcoming racial disparities in outcomes,” Dr. Barrington said.

The study was supported by the U.S. National Cancer Institute. Dr. Babic reported grants from the U.S. National Institutes of Health. Some coauthors reported grants from the NIH, the National Health and Medical Research Council of Australia, the Federal Ministry of Education and Research of Germany, the Danish Cancer Society, or the Mermaid I Project. Some coauthors had no disclosures to report. Dr. Barrington has no relevant relationships to disclose.

SOURCE: Babic A et al. JAMA Oncology. 2020. doi: 10.1001/jamaoncol.2020.0421.

Maternal preconception exposure to phthalates was associated with increased risk of preterm birth, according to a study of 420 births to subfertile couples over a 13-year period.

Previous studies have shown increased risk of preterm birth associated with prenatal exposure to phthalates, which are commonly found in a range of household and commercial products as well as medical equipment and some pharmaceuticals.

“Our results suggest that female exposure to [4 di(2-ethylhexyl) phthalate] DEHP before conception might be an unrecognized risk factor for adverse pregnancy outcomes, often overlooked in clinical practice,” wrote Yu Zhang of the department of environmental health at Harvard T.H. Chan School of Public Health, Boston, and colleagues.

The prospective cohort study evaluated preconception urinary levels of phthalates and phthalate substitutes in 419 women and 229 men participating in the Environment and Reproductive Health (EARTH) study, a cohort of couples seeking fertility care at the Massachusetts General Hospital Fertility Center. The study cohort gave birth during 2005-2018. The average gestational age of the 420 singleton children born to this cohort was 39 weeks, with 8% (n = 34) born preterm.

Adjusted models showed that maternal preconception urinary concentrations of phthalates and of cyclohexane-1, 2-dicarboxylic acid monohydroxy isononyl ester (MHiNCH), a metabolite of a nonphthalate plasticizer substitute, were associated with a 50% and 70% increased risk of preterm birth, respectively (P = .01, .11), according to results published in JAMA Network Open .

Sensitivity analysis showed that maternal preconception MHiNCH concentrations above the median were associated with a fourfold increased risk of preterm birth (risk ratio, 4.02; P = .08), Maternal preconception MHiNCH concentrations were associated with an average 2-day reduction in gestational age (P = .02).

Covariate-adjusted models found that paternal urinary phthalate metabolite concentrations were associated with an increased risk of preterm birth (RR, 1.41; P = .09), but this association was attenuated toward zero (RR, 1.06) in models that accounted for maternal preconception phthalate concentrations. Sensitivity analysis of 228 couples found the associations of maternal preconception phthalate metabolite concentrations and preterm birth remained robust in three different models: a twofold increased risk in covariate-adjusted models (P < .001); an almost fivefold increased risk in adjusting for prenatal levels (RR, 4.98; P < .001); and a twofold risk (P = .001) in adjusting for paternal levels. “Couple-based analyses confirmed the results for an association between maternal preconception DEHP concentrations and increased risk of preterm birth,” the investigators said.

“To our knowledge, this is the first study evaluating couples’ exposure to phthalate metabolites during the preconception window and its association with preterm birth,” the researchers wrote. “Our findings support a novel hypothesis: Maternal phthalate exposure during the critical period before conception may be associated with shorter gestation.”

“This study is consistent with several, but not all, prior studies supporting maternal prenatal exposure to phthalates increase preterm birth,” said Mark P. Trolice, MD, professor of obstetrics and gynecology at the University of Central Florida, Orlando. “The uniqueness of the current study was the assessment of couples’ exposures and the outcome, though paternal exposure to phthalates did not demonstrate a significant association.”

Dr. Trolice noted that about 25% of women in the study were smokers, but the study didn’t adjust for tobacco use and phthalate exposure, and 85% of the women were white. He urged caution in applying the study results in practice, adding that the study didn’t adjust for method of conception. “Assisted reproductive technology, multiple gestation, and advanced age are all known risk factors for preterm birth,”

The National Institute of Environmental Health Science funded the study. Two study coauthors received grants from the NIEHS, one coauthor received grants from the National Institutes of Health, and one received a grant from the Canadian Institutes of Health Research. No other disclosures were reported. Dr. Trolice has no financial relationships to disclose.

SOURCE: Zhang Y et al. JAMA Network Open. 2020; doi: 10.1001/jamanetworkopen.2020.2159.

Maternal preconception exposure to phthalates was associated with increased risk of preterm birth, according to a study of 420 births to subfertile couples over a 13-year period.

Previous studies have shown increased risk of preterm birth associated with prenatal exposure to phthalates, which are commonly found in a range of household and commercial products as well as medical equipment and some pharmaceuticals.

“Our results suggest that female exposure to [4 di(2-ethylhexyl) phthalate] DEHP before conception might be an unrecognized risk factor for adverse pregnancy outcomes, often overlooked in clinical practice,” wrote Yu Zhang of the department of environmental health at Harvard T.H. Chan School of Public Health, Boston, and colleagues.

The prospective cohort study evaluated preconception urinary levels of phthalates and phthalate substitutes in 419 women and 229 men participating in the Environment and Reproductive Health (EARTH) study, a cohort of couples seeking fertility care at the Massachusetts General Hospital Fertility Center. The study cohort gave birth during 2005-2018. The average gestational age of the 420 singleton children born to this cohort was 39 weeks, with 8% (n = 34) born preterm.

Adjusted models showed that maternal preconception urinary concentrations of phthalates and of cyclohexane-1, 2-dicarboxylic acid monohydroxy isononyl ester (MHiNCH), a metabolite of a nonphthalate plasticizer substitute, were associated with a 50% and 70% increased risk of preterm birth, respectively (P = .01, .11), according to results published in JAMA Network Open .

Sensitivity analysis showed that maternal preconception MHiNCH concentrations above the median were associated with a fourfold increased risk of preterm birth (risk ratio, 4.02; P = .08), Maternal preconception MHiNCH concentrations were associated with an average 2-day reduction in gestational age (P = .02).

Covariate-adjusted models found that paternal urinary phthalate metabolite concentrations were associated with an increased risk of preterm birth (RR, 1.41; P = .09), but this association was attenuated toward zero (RR, 1.06) in models that accounted for maternal preconception phthalate concentrations. Sensitivity analysis of 228 couples found the associations of maternal preconception phthalate metabolite concentrations and preterm birth remained robust in three different models: a twofold increased risk in covariate-adjusted models (P < .001); an almost fivefold increased risk in adjusting for prenatal levels (RR, 4.98; P < .001); and a twofold risk (P = .001) in adjusting for paternal levels. “Couple-based analyses confirmed the results for an association between maternal preconception DEHP concentrations and increased risk of preterm birth,” the investigators said.

“To our knowledge, this is the first study evaluating couples’ exposure to phthalate metabolites during the preconception window and its association with preterm birth,” the researchers wrote. “Our findings support a novel hypothesis: Maternal phthalate exposure during the critical period before conception may be associated with shorter gestation.”

“This study is consistent with several, but not all, prior studies supporting maternal prenatal exposure to phthalates increase preterm birth,” said Mark P. Trolice, MD, professor of obstetrics and gynecology at the University of Central Florida, Orlando. “The uniqueness of the current study was the assessment of couples’ exposures and the outcome, though paternal exposure to phthalates did not demonstrate a significant association.”

Dr. Trolice noted that about 25% of women in the study were smokers, but the study didn’t adjust for tobacco use and phthalate exposure, and 85% of the women were white. He urged caution in applying the study results in practice, adding that the study didn’t adjust for method of conception. “Assisted reproductive technology, multiple gestation, and advanced age are all known risk factors for preterm birth,”

The National Institute of Environmental Health Science funded the study. Two study coauthors received grants from the NIEHS, one coauthor received grants from the National Institutes of Health, and one received a grant from the Canadian Institutes of Health Research. No other disclosures were reported. Dr. Trolice has no financial relationships to disclose.

SOURCE: Zhang Y et al. JAMA Network Open. 2020; doi: 10.1001/jamanetworkopen.2020.2159.

Maternal preconception exposure to phthalates was associated with increased risk of preterm birth, according to a study of 420 births to subfertile couples over a 13-year period.

Previous studies have shown increased risk of preterm birth associated with prenatal exposure to phthalates, which are commonly found in a range of household and commercial products as well as medical equipment and some pharmaceuticals.

“Our results suggest that female exposure to [4 di(2-ethylhexyl) phthalate] DEHP before conception might be an unrecognized risk factor for adverse pregnancy outcomes, often overlooked in clinical practice,” wrote Yu Zhang of the department of environmental health at Harvard T.H. Chan School of Public Health, Boston, and colleagues.

The prospective cohort study evaluated preconception urinary levels of phthalates and phthalate substitutes in 419 women and 229 men participating in the Environment and Reproductive Health (EARTH) study, a cohort of couples seeking fertility care at the Massachusetts General Hospital Fertility Center. The study cohort gave birth during 2005-2018. The average gestational age of the 420 singleton children born to this cohort was 39 weeks, with 8% (n = 34) born preterm.

Adjusted models showed that maternal preconception urinary concentrations of phthalates and of cyclohexane-1, 2-dicarboxylic acid monohydroxy isononyl ester (MHiNCH), a metabolite of a nonphthalate plasticizer substitute, were associated with a 50% and 70% increased risk of preterm birth, respectively (P = .01, .11), according to results published in JAMA Network Open .

Sensitivity analysis showed that maternal preconception MHiNCH concentrations above the median were associated with a fourfold increased risk of preterm birth (risk ratio, 4.02; P = .08), Maternal preconception MHiNCH concentrations were associated with an average 2-day reduction in gestational age (P = .02).

Covariate-adjusted models found that paternal urinary phthalate metabolite concentrations were associated with an increased risk of preterm birth (RR, 1.41; P = .09), but this association was attenuated toward zero (RR, 1.06) in models that accounted for maternal preconception phthalate concentrations. Sensitivity analysis of 228 couples found the associations of maternal preconception phthalate metabolite concentrations and preterm birth remained robust in three different models: a twofold increased risk in covariate-adjusted models (P < .001); an almost fivefold increased risk in adjusting for prenatal levels (RR, 4.98; P < .001); and a twofold risk (P = .001) in adjusting for paternal levels. “Couple-based analyses confirmed the results for an association between maternal preconception DEHP concentrations and increased risk of preterm birth,” the investigators said.

“To our knowledge, this is the first study evaluating couples’ exposure to phthalate metabolites during the preconception window and its association with preterm birth,” the researchers wrote. “Our findings support a novel hypothesis: Maternal phthalate exposure during the critical period before conception may be associated with shorter gestation.”

“This study is consistent with several, but not all, prior studies supporting maternal prenatal exposure to phthalates increase preterm birth,” said Mark P. Trolice, MD, professor of obstetrics and gynecology at the University of Central Florida, Orlando. “The uniqueness of the current study was the assessment of couples’ exposures and the outcome, though paternal exposure to phthalates did not demonstrate a significant association.”

Dr. Trolice noted that about 25% of women in the study were smokers, but the study didn’t adjust for tobacco use and phthalate exposure, and 85% of the women were white. He urged caution in applying the study results in practice, adding that the study didn’t adjust for method of conception. “Assisted reproductive technology, multiple gestation, and advanced age are all known risk factors for preterm birth,”

The National Institute of Environmental Health Science funded the study. Two study coauthors received grants from the NIEHS, one coauthor received grants from the National Institutes of Health, and one received a grant from the Canadian Institutes of Health Research. No other disclosures were reported. Dr. Trolice has no financial relationships to disclose.

SOURCE: Zhang Y et al. JAMA Network Open. 2020; doi: 10.1001/jamanetworkopen.2020.2159.

Almost all patients who develop gastrointestinal side effects from oral immunotherapy for severe food allergies develop some degree of esophageal eosinophilia, but that eventually resolves in most of them after a year of treatment, according to results of a pilot study that was to be presented at the American Academy of Allergy, Asthma & Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

The findings may help identify biomarkers of persistent eosinophilia despite oral immunotherapy.

In January of this year the Food and Drug Administration approved oral immunotherapy (OIT), known as peanut allergen powder-dnfp, or peanut OIT (POIT), for severe food allergies. In an interview, lead study author Benjamin Wright, MD, of the Mayo Clinic, Phoenix, said OIT is a “promising proactive” treatment for food allergies. “But questions regarding the safety of immunotherapy remain,” he said. “About 30% of patients can develop GI side effects, including abdominal pain and vomiting; most concerning is that some patients develop eosinophilic esophagitis (EoE).”

The pilot study was a mechanistic substudy of 20 adult patients with immunoglobulin E–mediated peanut allergies enrolled in the phase 2 Peanut Oral Immunotherapy Safety, Efficacy and Discovery trial (POISED), with 15 randomized to treatment and the remainder to placebo. They had serial gastrointestinal biopsies at baseline (n = 20), 1 year (n = 7 treatment, 3 placebo) and 2 years (n = 7 treatment, 4 placebo) to evaluate eosinophils per high-power field (eos/hpf).

Baseline characteristics between the treatment and placebo groups were similar, with some having signs of preexisting disease. About 14% of them had clinically significant EoE, represented as a measure of more than 15 eos/hpf, Dr. Wright said. “One of the findings that was really fascinating to us was that all of the subjects had evidence of dilated intercellular spaces at baseline,” he said. “This indicates that all the subjects have some degree of epithelial barrier dysfunction before they start OIT.” Dilated intercellular spaces are a marker of inflammation.

Four patients in the treatment group had mild endoscopic findings at weeks 52 and 104, as did one patient on placebo, Dr. Wright said. A plot of eosinophil counts showed a peak at 52 weeks but near resolution at 104 weeks for all but one patient on OIT. “One of the most interesting trends that we noted was that, for most of patients, OIT-induced eosinophilia was transient and not fixed,” he said. “We noted a triangle pattern where tissue eosinophilia peaks and then resolves with the continuation of therapy.” EoE Histologic scoring system results followed a similar pattern in these patients, he added.

Also, results of the comprehensive GI Symptom Questionnaire, which assessed symptoms such as abdominal pain, difficulty swallowing, refusal to eat, and vomiting, showed that patient-reported GI symptoms did not correlate with tissue eosinophilia, Dr. Wright said. “To us, that suggests that perhaps eosinophils are not central to disease pathology or symptom development in these patients,” he said.

However, the findings validate that, in a small number of patients, OIT induces EoE, Dr. Wright said. He used a treadmill analogy to explain how OIT influences epithelial remodeling in some patients. “We’re constantly renewing our esophageal epithelium every 2 weeks, and when you challenge it with an antigen (i.e., OIT), the treadmill speeds up,” he said. “There may be some patients who will fall if the treadmill gets too fast, and they develop disease.”

He added, “Distinguishing someone’s fitness before they get on the treadmill is really going be a key moving forward in determining which subjects are good participants for OIT or how to dose OIT.”

Dr. Wright reported receiving grants from the Arizona Biomedical Research Consortium and Phoenix Children’s Hospital Foundation. Coauthors reported receiving grants from the National Institutes of Health and the Consortium for Food Allergy Research, as well as relationships with Aimmune Therapeutics, Regeneron Pharmaceuticals, Sanofi, Consortium for Food Allergy Research, DBV Technologies, Astellas, AnaptysBio, and Novartis.

SOURCE: Wright B et al. AAAAI, Session 2605, Abstract No. 259.

Almost all patients who develop gastrointestinal side effects from oral immunotherapy for severe food allergies develop some degree of esophageal eosinophilia, but that eventually resolves in most of them after a year of treatment, according to results of a pilot study that was to be presented at the American Academy of Allergy, Asthma & Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

The findings may help identify biomarkers of persistent eosinophilia despite oral immunotherapy.

In January of this year the Food and Drug Administration approved oral immunotherapy (OIT), known as peanut allergen powder-dnfp, or peanut OIT (POIT), for severe food allergies. In an interview, lead study author Benjamin Wright, MD, of the Mayo Clinic, Phoenix, said OIT is a “promising proactive” treatment for food allergies. “But questions regarding the safety of immunotherapy remain,” he said. “About 30% of patients can develop GI side effects, including abdominal pain and vomiting; most concerning is that some patients develop eosinophilic esophagitis (EoE).”

The pilot study was a mechanistic substudy of 20 adult patients with immunoglobulin E–mediated peanut allergies enrolled in the phase 2 Peanut Oral Immunotherapy Safety, Efficacy and Discovery trial (POISED), with 15 randomized to treatment and the remainder to placebo. They had serial gastrointestinal biopsies at baseline (n = 20), 1 year (n = 7 treatment, 3 placebo) and 2 years (n = 7 treatment, 4 placebo) to evaluate eosinophils per high-power field (eos/hpf).

Baseline characteristics between the treatment and placebo groups were similar, with some having signs of preexisting disease. About 14% of them had clinically significant EoE, represented as a measure of more than 15 eos/hpf, Dr. Wright said. “One of the findings that was really fascinating to us was that all of the subjects had evidence of dilated intercellular spaces at baseline,” he said. “This indicates that all the subjects have some degree of epithelial barrier dysfunction before they start OIT.” Dilated intercellular spaces are a marker of inflammation.

Four patients in the treatment group had mild endoscopic findings at weeks 52 and 104, as did one patient on placebo, Dr. Wright said. A plot of eosinophil counts showed a peak at 52 weeks but near resolution at 104 weeks for all but one patient on OIT. “One of the most interesting trends that we noted was that, for most of patients, OIT-induced eosinophilia was transient and not fixed,” he said. “We noted a triangle pattern where tissue eosinophilia peaks and then resolves with the continuation of therapy.” EoE Histologic scoring system results followed a similar pattern in these patients, he added.

Also, results of the comprehensive GI Symptom Questionnaire, which assessed symptoms such as abdominal pain, difficulty swallowing, refusal to eat, and vomiting, showed that patient-reported GI symptoms did not correlate with tissue eosinophilia, Dr. Wright said. “To us, that suggests that perhaps eosinophils are not central to disease pathology or symptom development in these patients,” he said.

However, the findings validate that, in a small number of patients, OIT induces EoE, Dr. Wright said. He used a treadmill analogy to explain how OIT influences epithelial remodeling in some patients. “We’re constantly renewing our esophageal epithelium every 2 weeks, and when you challenge it with an antigen (i.e., OIT), the treadmill speeds up,” he said. “There may be some patients who will fall if the treadmill gets too fast, and they develop disease.”

He added, “Distinguishing someone’s fitness before they get on the treadmill is really going be a key moving forward in determining which subjects are good participants for OIT or how to dose OIT.”

Dr. Wright reported receiving grants from the Arizona Biomedical Research Consortium and Phoenix Children’s Hospital Foundation. Coauthors reported receiving grants from the National Institutes of Health and the Consortium for Food Allergy Research, as well as relationships with Aimmune Therapeutics, Regeneron Pharmaceuticals, Sanofi, Consortium for Food Allergy Research, DBV Technologies, Astellas, AnaptysBio, and Novartis.

SOURCE: Wright B et al. AAAAI, Session 2605, Abstract No. 259.

Almost all patients who develop gastrointestinal side effects from oral immunotherapy for severe food allergies develop some degree of esophageal eosinophilia, but that eventually resolves in most of them after a year of treatment, according to results of a pilot study that was to be presented at the American Academy of Allergy, Asthma & Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

The findings may help identify biomarkers of persistent eosinophilia despite oral immunotherapy.

In January of this year the Food and Drug Administration approved oral immunotherapy (OIT), known as peanut allergen powder-dnfp, or peanut OIT (POIT), for severe food allergies. In an interview, lead study author Benjamin Wright, MD, of the Mayo Clinic, Phoenix, said OIT is a “promising proactive” treatment for food allergies. “But questions regarding the safety of immunotherapy remain,” he said. “About 30% of patients can develop GI side effects, including abdominal pain and vomiting; most concerning is that some patients develop eosinophilic esophagitis (EoE).”

The pilot study was a mechanistic substudy of 20 adult patients with immunoglobulin E–mediated peanut allergies enrolled in the phase 2 Peanut Oral Immunotherapy Safety, Efficacy and Discovery trial (POISED), with 15 randomized to treatment and the remainder to placebo. They had serial gastrointestinal biopsies at baseline (n = 20), 1 year (n = 7 treatment, 3 placebo) and 2 years (n = 7 treatment, 4 placebo) to evaluate eosinophils per high-power field (eos/hpf).

Baseline characteristics between the treatment and placebo groups were similar, with some having signs of preexisting disease. About 14% of them had clinically significant EoE, represented as a measure of more than 15 eos/hpf, Dr. Wright said. “One of the findings that was really fascinating to us was that all of the subjects had evidence of dilated intercellular spaces at baseline,” he said. “This indicates that all the subjects have some degree of epithelial barrier dysfunction before they start OIT.” Dilated intercellular spaces are a marker of inflammation.

Four patients in the treatment group had mild endoscopic findings at weeks 52 and 104, as did one patient on placebo, Dr. Wright said. A plot of eosinophil counts showed a peak at 52 weeks but near resolution at 104 weeks for all but one patient on OIT. “One of the most interesting trends that we noted was that, for most of patients, OIT-induced eosinophilia was transient and not fixed,” he said. “We noted a triangle pattern where tissue eosinophilia peaks and then resolves with the continuation of therapy.” EoE Histologic scoring system results followed a similar pattern in these patients, he added.

Also, results of the comprehensive GI Symptom Questionnaire, which assessed symptoms such as abdominal pain, difficulty swallowing, refusal to eat, and vomiting, showed that patient-reported GI symptoms did not correlate with tissue eosinophilia, Dr. Wright said. “To us, that suggests that perhaps eosinophils are not central to disease pathology or symptom development in these patients,” he said.

However, the findings validate that, in a small number of patients, OIT induces EoE, Dr. Wright said. He used a treadmill analogy to explain how OIT influences epithelial remodeling in some patients. “We’re constantly renewing our esophageal epithelium every 2 weeks, and when you challenge it with an antigen (i.e., OIT), the treadmill speeds up,” he said. “There may be some patients who will fall if the treadmill gets too fast, and they develop disease.”

He added, “Distinguishing someone’s fitness before they get on the treadmill is really going be a key moving forward in determining which subjects are good participants for OIT or how to dose OIT.”

Dr. Wright reported receiving grants from the Arizona Biomedical Research Consortium and Phoenix Children’s Hospital Foundation. Coauthors reported receiving grants from the National Institutes of Health and the Consortium for Food Allergy Research, as well as relationships with Aimmune Therapeutics, Regeneron Pharmaceuticals, Sanofi, Consortium for Food Allergy Research, DBV Technologies, Astellas, AnaptysBio, and Novartis.

SOURCE: Wright B et al. AAAAI, Session 2605, Abstract No. 259.

A small-molecule kinase inhibitor that targets a gene mutation complicit in systemic mastocytosis has been found to reduce symptoms by about 30%, according to early results of a clinical trial scheduled to be presented at the American Academy of Allergy, Asthma, and Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

“This correlates with reduction from very severe to moderate or from moderate to mild category, and all the reductions in symptoms were statistically significant,” Cem Akin, MD, of the University of Michigan, Ann Arbor, said in an interview. He reported on part 1 of the phase 2 PIONEER trial of the kinase inhibitor avapritinib, described as a potent and highly selective inhibitor of the KIT D816V mutation that affects 90% of patients with systemic mastocytosis.

Currently, Dr. Akin noted, patients with indolent or smoldering systemic mastocytosis must rely on over-the-counter antihistamines used for seasonal allergies. “These patients use antihistamines in higher doses because mastocytosis patients have higher counts of mast cells that release histamines that cause a variety of symptoms,” he said. Symptoms, which can occur suddenly, include flushing and reactions that resemble allergic or anaphylactic reactions.

The purpose of the part 1 study was to evaluate three different dosing levels of avapritinib vs. placebo: 25, 50, and 100 mg. Ten patients were in each dosing group and nine were in the placebo group. The primary outcome was reduction in total symptom scores at 16 weeks as measured by the Indolent SM Symptom Assessment Form. “All three dose groups showed significant reductions in total symptom scores as well as specific symptoms that were most bothersome to the patient, whether skin symptoms or GI or neurocognitive symptoms,” Dr. Akin said. “All three doses were effective; the average reduction was about 30% compared to baseline.” Specifically, 25-mg dosing showed an average 30% reduction, 50-mg dosing showed an average 19% reduction, and 100-mg dosing showed an average 35% reduction.

The researchers determined that the 25-mg daily dose was the most effective and safest, with no patients on the dose reporting grade 3 adverse events, Dr. Akin said. In total 20% and 40% of the 50- and 100-mg dose groups, respectively, reported grade 3 AEs, according to study results.* The 25-mg daily dose will be evaluated in part 2 of the trial. The trial is estimated to enroll 112 total patients, according to the ClinicalTrials.gov filing. In part 3, patients who complete parts 1 or 2, including those initially randomized to placebo, may participate in a long-term open-label extension, receiving 25 mg avapritinib plus best supportive care.

“This is targeting a population whose symptoms are not controlled by antihistamines, based on a minimum total symptom score according to diaries they fill out, and they have to be on at least two different systemic medications – antihistamine or proton-pump inhibitor and leukotriene inhibitor – and they still have significant symptoms,” Dr. Akin said. He estimated that this describes about two-thirds of his patients with indolent or smoldering systematic mastocytosis.

“This is a disease that also takes a psychological toll,” he said. “This is a problem that starts in the bone marrow; it is similar to a hematological stem-cell disorder that affects the mast cell progenitor and it’s caused by a mutation that has not been particularly targeted until this drug,” he said. While most of these patients live with a benign mastocytosis their entire lives, the symptoms can be debilitating to the point where the disease disrupts and restricts social activities and comprises their quality of life, he said.

“This is a groundbreaking therapy that will change the way we think about mastocytosis treatment going forward,” Dr. Akin said. “It’s the first time we are actually targeting the underlying mutation that’s causing the disease, in terms of reducing directly that mutation as opposed to just treating the symptoms in indolent disease.”

Scheduled session moderator Anil Nanda, MD, of the Asthma and Allergy Center in Lewisville, Texas, said the findings are encouraging. “As a practicing allergist and immunologist in the community, it is very exciting to have a potential new treatment option for indolent or smoldering systemic mastocytosis,” he said via email. “Patients appreciate new options in therapy.”

Dr. Akin, the primary investigator, receives funding from and serves as a consultant for Blueprint Medicines, which sponsored the trial. He also disclosed a financial relationship with Novartis.

SOURCE: Akin C et al. AAAAI 2020, Presentation L5.

*Correction, 4/6/2020: An earlier version of this story misstated the percentage of grade 3 adverse events. In total 20% and 40% of the 50- and 100-mg dose groups, respectively, reported grade 3 adverse events.  

A small-molecule kinase inhibitor that targets a gene mutation complicit in systemic mastocytosis has been found to reduce symptoms by about 30%, according to early results of a clinical trial scheduled to be presented at the American Academy of Allergy, Asthma, and Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

“This correlates with reduction from very severe to moderate or from moderate to mild category, and all the reductions in symptoms were statistically significant,” Cem Akin, MD, of the University of Michigan, Ann Arbor, said in an interview. He reported on part 1 of the phase 2 PIONEER trial of the kinase inhibitor avapritinib, described as a potent and highly selective inhibitor of the KIT D816V mutation that affects 90% of patients with systemic mastocytosis.

Currently, Dr. Akin noted, patients with indolent or smoldering systemic mastocytosis must rely on over-the-counter antihistamines used for seasonal allergies. “These patients use antihistamines in higher doses because mastocytosis patients have higher counts of mast cells that release histamines that cause a variety of symptoms,” he said. Symptoms, which can occur suddenly, include flushing and reactions that resemble allergic or anaphylactic reactions.

The purpose of the part 1 study was to evaluate three different dosing levels of avapritinib vs. placebo: 25, 50, and 100 mg. Ten patients were in each dosing group and nine were in the placebo group. The primary outcome was reduction in total symptom scores at 16 weeks as measured by the Indolent SM Symptom Assessment Form. “All three dose groups showed significant reductions in total symptom scores as well as specific symptoms that were most bothersome to the patient, whether skin symptoms or GI or neurocognitive symptoms,” Dr. Akin said. “All three doses were effective; the average reduction was about 30% compared to baseline.” Specifically, 25-mg dosing showed an average 30% reduction, 50-mg dosing showed an average 19% reduction, and 100-mg dosing showed an average 35% reduction.

The researchers determined that the 25-mg daily dose was the most effective and safest, with no patients on the dose reporting grade 3 adverse events, Dr. Akin said. In total 20% and 40% of the 50- and 100-mg dose groups, respectively, reported grade 3 AEs, according to study results.* The 25-mg daily dose will be evaluated in part 2 of the trial. The trial is estimated to enroll 112 total patients, according to the ClinicalTrials.gov filing. In part 3, patients who complete parts 1 or 2, including those initially randomized to placebo, may participate in a long-term open-label extension, receiving 25 mg avapritinib plus best supportive care.

“This is targeting a population whose symptoms are not controlled by antihistamines, based on a minimum total symptom score according to diaries they fill out, and they have to be on at least two different systemic medications – antihistamine or proton-pump inhibitor and leukotriene inhibitor – and they still have significant symptoms,” Dr. Akin said. He estimated that this describes about two-thirds of his patients with indolent or smoldering systematic mastocytosis.

“This is a disease that also takes a psychological toll,” he said. “This is a problem that starts in the bone marrow; it is similar to a hematological stem-cell disorder that affects the mast cell progenitor and it’s caused by a mutation that has not been particularly targeted until this drug,” he said. While most of these patients live with a benign mastocytosis their entire lives, the symptoms can be debilitating to the point where the disease disrupts and restricts social activities and comprises their quality of life, he said.

“This is a groundbreaking therapy that will change the way we think about mastocytosis treatment going forward,” Dr. Akin said. “It’s the first time we are actually targeting the underlying mutation that’s causing the disease, in terms of reducing directly that mutation as opposed to just treating the symptoms in indolent disease.”

Scheduled session moderator Anil Nanda, MD, of the Asthma and Allergy Center in Lewisville, Texas, said the findings are encouraging. “As a practicing allergist and immunologist in the community, it is very exciting to have a potential new treatment option for indolent or smoldering systemic mastocytosis,” he said via email. “Patients appreciate new options in therapy.”

Dr. Akin, the primary investigator, receives funding from and serves as a consultant for Blueprint Medicines, which sponsored the trial. He also disclosed a financial relationship with Novartis.

SOURCE: Akin C et al. AAAAI 2020, Presentation L5.

*Correction, 4/6/2020: An earlier version of this story misstated the percentage of grade 3 adverse events. In total 20% and 40% of the 50- and 100-mg dose groups, respectively, reported grade 3 adverse events.  

A small-molecule kinase inhibitor that targets a gene mutation complicit in systemic mastocytosis has been found to reduce symptoms by about 30%, according to early results of a clinical trial scheduled to be presented at the American Academy of Allergy, Asthma, and Immunology annual meeting. The AAAAI canceled the meeting and provided abstracts and access to presenters for press coverage.

“This correlates with reduction from very severe to moderate or from moderate to mild category, and all the reductions in symptoms were statistically significant,” Cem Akin, MD, of the University of Michigan, Ann Arbor, said in an interview. He reported on part 1 of the phase 2 PIONEER trial of the kinase inhibitor avapritinib, described as a potent and highly selective inhibitor of the KIT D816V mutation that affects 90% of patients with systemic mastocytosis.

Currently, Dr. Akin noted, patients with indolent or smoldering systemic mastocytosis must rely on over-the-counter antihistamines used for seasonal allergies. “These patients use antihistamines in higher doses because mastocytosis patients have higher counts of mast cells that release histamines that cause a variety of symptoms,” he said. Symptoms, which can occur suddenly, include flushing and reactions that resemble allergic or anaphylactic reactions.

The purpose of the part 1 study was to evaluate three different dosing levels of avapritinib vs. placebo: 25, 50, and 100 mg. Ten patients were in each dosing group and nine were in the placebo group. The primary outcome was reduction in total symptom scores at 16 weeks as measured by the Indolent SM Symptom Assessment Form. “All three dose groups showed significant reductions in total symptom scores as well as specific symptoms that were most bothersome to the patient, whether skin symptoms or GI or neurocognitive symptoms,” Dr. Akin said. “All three doses were effective; the average reduction was about 30% compared to baseline.” Specifically, 25-mg dosing showed an average 30% reduction, 50-mg dosing showed an average 19% reduction, and 100-mg dosing showed an average 35% reduction.

The researchers determined that the 25-mg daily dose was the most effective and safest, with no patients on the dose reporting grade 3 adverse events, Dr. Akin said. In total 20% and 40% of the 50- and 100-mg dose groups, respectively, reported grade 3 AEs, according to study results.* The 25-mg daily dose will be evaluated in part 2 of the trial. The trial is estimated to enroll 112 total patients, according to the ClinicalTrials.gov filing. In part 3, patients who complete parts 1 or 2, including those initially randomized to placebo, may participate in a long-term open-label extension, receiving 25 mg avapritinib plus best supportive care.

“This is targeting a population whose symptoms are not controlled by antihistamines, based on a minimum total symptom score according to diaries they fill out, and they have to be on at least two different systemic medications – antihistamine or proton-pump inhibitor and leukotriene inhibitor – and they still have significant symptoms,” Dr. Akin said. He estimated that this describes about two-thirds of his patients with indolent or smoldering systematic mastocytosis.

“This is a disease that also takes a psychological toll,” he said. “This is a problem that starts in the bone marrow; it is similar to a hematological stem-cell disorder that affects the mast cell progenitor and it’s caused by a mutation that has not been particularly targeted until this drug,” he said. While most of these patients live with a benign mastocytosis their entire lives, the symptoms can be debilitating to the point where the disease disrupts and restricts social activities and comprises their quality of life, he said.

“This is a groundbreaking therapy that will change the way we think about mastocytosis treatment going forward,” Dr. Akin said. “It’s the first time we are actually targeting the underlying mutation that’s causing the disease, in terms of reducing directly that mutation as opposed to just treating the symptoms in indolent disease.”

Scheduled session moderator Anil Nanda, MD, of the Asthma and Allergy Center in Lewisville, Texas, said the findings are encouraging. “As a practicing allergist and immunologist in the community, it is very exciting to have a potential new treatment option for indolent or smoldering systemic mastocytosis,” he said via email. “Patients appreciate new options in therapy.”

Dr. Akin, the primary investigator, receives funding from and serves as a consultant for Blueprint Medicines, which sponsored the trial. He also disclosed a financial relationship with Novartis.

SOURCE: Akin C et al. AAAAI 2020, Presentation L5.

*Correction, 4/6/2020: An earlier version of this story misstated the percentage of grade 3 adverse events. In total 20% and 40% of the 50- and 100-mg dose groups, respectively, reported grade 3 adverse events.  

Insurance and specialty pharmacy delays in authorizing new biologic prescriptions for severe allergies leave waiting patients at risk of asthma attacks, hospitalizations, emergency department visits and prednisone shots and their known side effects, according to a single-center study that was to have been presented at the annual meeting of the American Academy of Allergy, Asthma and Immunology.

The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.

The study of 80 patients in State College, Pa., found that they waited an average of 44 days from when their doctor submitted the preauthorization request to the insurance company until the practice received the shipment for dispensing to the patient, investigator Faoud Ishmael, MD, PhD, of Mount Nittany Medical Group said in an interview. “The implication here is that these are really the most severe patients who, you would argue, need their medications the quickest, and it’s taking longer to get them than it would an inhaler,” Dr. Ishmael said.

The study focused on patients with severe asthma (n = 60) or urticarial (n = 20) who received a new prescription of monoclonal antibody therapy from March 2014 to August 2019. For asthma treatments, the average time was 45.8 days; for urticaria, 40.6 days (P = .573), Dr. Ishmael said. The researchers divided the total amount of time into two components: insurance plan review and approval (P = .654, and specialty pharmacy review and dispensing of the medicine, each of which averaged 22.8 days (P = .384), he said.

He also noted wide disparity in the range of approval times. “The shortest approval time was 1 day, and the longest 97 days,” Dr. Ishmael said. “It’s interesting that we had this really broad spread.”

What’s more, the study found no trend for the delays among insurers and specialty pharmacies, Dr. Ishmael added. “When these prescriptions get submitted, it’s like a black box,” he said. “It really seems arbitrary why some of them take so long and some of them don’t.” The findings were independent of type of coverage, whether commercial or government, or even specific insurance plans. “It’s more the process that is flawed rather than one insurance company being the bad guy,” he said.

The study also looked at what happened to patients while they were waiting for their prescriptions to be delivered. “What we found is that over half of asthmatics had an exacerbation – 51% had at least one asthma attack where they needed prednisone,” Dr. Ishmael said (P = .0015), “and we had three patients admitted to the hospital over that time frame when they were waiting for the drugs.” One of those patients had been admitted twice, making four total hospitalizations. Preliminary data analysis showed that about 40% of the patients who had attacks went to the emergency department.

For asthmatics who needed prednisone, the average dose was 480 mg (P = .284) – “a pretty substantial number,” in Dr. Ishmael’s words. He noted that a large portion of the study patients were obese, with a mean body mass index of 33 kg/m². Other comorbidities prevalent in the study population were hypertension and type 2 diabetes. “Prednisone is something that could worsen all of those conditions, so it’s not a trivial issue,” he said.

The study, however, didn’t evaluate costs of the interventions during the delay period vs. the costs of the medications themselves. Of the 80 prescriptions Dr. Ishmael and coauthors submitted, only one was rejected, that person being a smoker, he said. “I understand these are expensive medicines, but it’s counterproductive to delay them because in the long run the insurance company ends up paying for the hospitalization and the drug rather than just the drug,” he said.

Timothy Craig, DO, of Penn State Health Allergy, Asthma, and Immunology and professor of medicine and pediatrics at Penn State College of Medicine, both in Hershey, said he was surprised at the brevity of the delays reported in Dr. Ishmael’s study. “They do much better than we do with preauthorization,” he said, noting that, in his experience, these approvals take much longer. He added that his own research has found faulty insurance plan algorithms are at the heart of these delays. “We need more studies to clarify how much this is interfering with patient care and how much risk they’re putting patients in,” he said.

The COVID-19 pandemic poses a double-edged sword for physicians managing patients with severe asthma, Dr. Craig noted. “Their asthma care is important, especially if they do test for COVID-19,” he said. On the other hand, doctors and nurses attending to COVID-19 patients will have less time to haggle with payers to expedite coverage for biologics for their severe asthma patients, he said. “I hope the flexibility is there, especially at this time to allow people to get on the biologics and stay on them,” he said.

Dr. Ishmael said these findings have serious implications because biologics are getting prescribed ever more frequently for asthma and hives. Steps his practice has taken to streamline the process include following the payer’s approval guidelines as closely as possible. This sometimes can mean making sure a patient with severe asthma has been maximized on controller medications before submitting the biologic prescription, he said. Another step is to use drug company programs to remove barriers to coverage.

Nonetheless, the approval process can be daunting even when taking those steps, he said. “Those guidelines that constitute approval may vary a lot from one insurer to another; and sometimes those guidelines are different from the criteria that studies may have used when these drugs were being evaluated in clinical trials,” he said. It would be helpful, he said, if payers used the National Heart, Lung and Blood institute and the Global Initiative for Asthma guidelines for biologics.

One of the goals of the researchers is to present their findings to payers, “to let them know, here are some of the hang-ups and the real risks associated with delaying these medications,” Dr. Ishmael said.

“When specialists especially prescribe these therapies, there’s usually a valid reason,” he said. “We really need to do something about the current process – if there are ways to make it more transparent, faster.”

Dr. Ishmael has no relevant financial relationships to disclose.

SOURCE: Ishmael F et al. AAAAI 2020. Session 3609, Presentation 558.

Insurance and specialty pharmacy delays in authorizing new biologic prescriptions for severe allergies leave waiting patients at risk of asthma attacks, hospitalizations, emergency department visits and prednisone shots and their known side effects, according to a single-center study that was to have been presented at the annual meeting of the American Academy of Allergy, Asthma and Immunology.

The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.

The study of 80 patients in State College, Pa., found that they waited an average of 44 days from when their doctor submitted the preauthorization request to the insurance company until the practice received the shipment for dispensing to the patient, investigator Faoud Ishmael, MD, PhD, of Mount Nittany Medical Group said in an interview. “The implication here is that these are really the most severe patients who, you would argue, need their medications the quickest, and it’s taking longer to get them than it would an inhaler,” Dr. Ishmael said.

The study focused on patients with severe asthma (n = 60) or urticarial (n = 20) who received a new prescription of monoclonal antibody therapy from March 2014 to August 2019. For asthma treatments, the average time was 45.8 days; for urticaria, 40.6 days (P = .573), Dr. Ishmael said. The researchers divided the total amount of time into two components: insurance plan review and approval (P = .654, and specialty pharmacy review and dispensing of the medicine, each of which averaged 22.8 days (P = .384), he said.

He also noted wide disparity in the range of approval times. “The shortest approval time was 1 day, and the longest 97 days,” Dr. Ishmael said. “It’s interesting that we had this really broad spread.”

What’s more, the study found no trend for the delays among insurers and specialty pharmacies, Dr. Ishmael added. “When these prescriptions get submitted, it’s like a black box,” he said. “It really seems arbitrary why some of them take so long and some of them don’t.” The findings were independent of type of coverage, whether commercial or government, or even specific insurance plans. “It’s more the process that is flawed rather than one insurance company being the bad guy,” he said.

The study also looked at what happened to patients while they were waiting for their prescriptions to be delivered. “What we found is that over half of asthmatics had an exacerbation – 51% had at least one asthma attack where they needed prednisone,” Dr. Ishmael said (P = .0015), “and we had three patients admitted to the hospital over that time frame when they were waiting for the drugs.” One of those patients had been admitted twice, making four total hospitalizations. Preliminary data analysis showed that about 40% of the patients who had attacks went to the emergency department.

For asthmatics who needed prednisone, the average dose was 480 mg (P = .284) – “a pretty substantial number,” in Dr. Ishmael’s words. He noted that a large portion of the study patients were obese, with a mean body mass index of 33 kg/m². Other comorbidities prevalent in the study population were hypertension and type 2 diabetes. “Prednisone is something that could worsen all of those conditions, so it’s not a trivial issue,” he said.

The study, however, didn’t evaluate costs of the interventions during the delay period vs. the costs of the medications themselves. Of the 80 prescriptions Dr. Ishmael and coauthors submitted, only one was rejected, that person being a smoker, he said. “I understand these are expensive medicines, but it’s counterproductive to delay them because in the long run the insurance company ends up paying for the hospitalization and the drug rather than just the drug,” he said.

Timothy Craig, DO, of Penn State Health Allergy, Asthma, and Immunology and professor of medicine and pediatrics at Penn State College of Medicine, both in Hershey, said he was surprised at the brevity of the delays reported in Dr. Ishmael’s study. “They do much better than we do with preauthorization,” he said, noting that, in his experience, these approvals take much longer. He added that his own research has found faulty insurance plan algorithms are at the heart of these delays. “We need more studies to clarify how much this is interfering with patient care and how much risk they’re putting patients in,” he said.

The COVID-19 pandemic poses a double-edged sword for physicians managing patients with severe asthma, Dr. Craig noted. “Their asthma care is important, especially if they do test for COVID-19,” he said. On the other hand, doctors and nurses attending to COVID-19 patients will have less time to haggle with payers to expedite coverage for biologics for their severe asthma patients, he said. “I hope the flexibility is there, especially at this time to allow people to get on the biologics and stay on them,” he said.

Dr. Ishmael said these findings have serious implications because biologics are getting prescribed ever more frequently for asthma and hives. Steps his practice has taken to streamline the process include following the payer’s approval guidelines as closely as possible. This sometimes can mean making sure a patient with severe asthma has been maximized on controller medications before submitting the biologic prescription, he said. Another step is to use drug company programs to remove barriers to coverage.

Nonetheless, the approval process can be daunting even when taking those steps, he said. “Those guidelines that constitute approval may vary a lot from one insurer to another; and sometimes those guidelines are different from the criteria that studies may have used when these drugs were being evaluated in clinical trials,” he said. It would be helpful, he said, if payers used the National Heart, Lung and Blood institute and the Global Initiative for Asthma guidelines for biologics.

One of the goals of the researchers is to present their findings to payers, “to let them know, here are some of the hang-ups and the real risks associated with delaying these medications,” Dr. Ishmael said.

“When specialists especially prescribe these therapies, there’s usually a valid reason,” he said. “We really need to do something about the current process – if there are ways to make it more transparent, faster.”

Dr. Ishmael has no relevant financial relationships to disclose.

SOURCE: Ishmael F et al. AAAAI 2020. Session 3609, Presentation 558.

Insurance and specialty pharmacy delays in authorizing new biologic prescriptions for severe allergies leave waiting patients at risk of asthma attacks, hospitalizations, emergency department visits and prednisone shots and their known side effects, according to a single-center study that was to have been presented at the annual meeting of the American Academy of Allergy, Asthma and Immunology.

The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.

The study of 80 patients in State College, Pa., found that they waited an average of 44 days from when their doctor submitted the preauthorization request to the insurance company until the practice received the shipment for dispensing to the patient, investigator Faoud Ishmael, MD, PhD, of Mount Nittany Medical Group said in an interview. “The implication here is that these are really the most severe patients who, you would argue, need their medications the quickest, and it’s taking longer to get them than it would an inhaler,” Dr. Ishmael said.

The study focused on patients with severe asthma (n = 60) or urticarial (n = 20) who received a new prescription of monoclonal antibody therapy from March 2014 to August 2019. For asthma treatments, the average time was 45.8 days; for urticaria, 40.6 days (P = .573), Dr. Ishmael said. The researchers divided the total amount of time into two components: insurance plan review and approval (P = .654, and specialty pharmacy review and dispensing of the medicine, each of which averaged 22.8 days (P = .384), he said.

He also noted wide disparity in the range of approval times. “The shortest approval time was 1 day, and the longest 97 days,” Dr. Ishmael said. “It’s interesting that we had this really broad spread.”

What’s more, the study found no trend for the delays among insurers and specialty pharmacies, Dr. Ishmael added. “When these prescriptions get submitted, it’s like a black box,” he said. “It really seems arbitrary why some of them take so long and some of them don’t.” The findings were independent of type of coverage, whether commercial or government, or even specific insurance plans. “It’s more the process that is flawed rather than one insurance company being the bad guy,” he said.

The study also looked at what happened to patients while they were waiting for their prescriptions to be delivered. “What we found is that over half of asthmatics had an exacerbation – 51% had at least one asthma attack where they needed prednisone,” Dr. Ishmael said (P = .0015), “and we had three patients admitted to the hospital over that time frame when they were waiting for the drugs.” One of those patients had been admitted twice, making four total hospitalizations. Preliminary data analysis showed that about 40% of the patients who had attacks went to the emergency department.

For asthmatics who needed prednisone, the average dose was 480 mg (P = .284) – “a pretty substantial number,” in Dr. Ishmael’s words. He noted that a large portion of the study patients were obese, with a mean body mass index of 33 kg/m². Other comorbidities prevalent in the study population were hypertension and type 2 diabetes. “Prednisone is something that could worsen all of those conditions, so it’s not a trivial issue,” he said.

The study, however, didn’t evaluate costs of the interventions during the delay period vs. the costs of the medications themselves. Of the 80 prescriptions Dr. Ishmael and coauthors submitted, only one was rejected, that person being a smoker, he said. “I understand these are expensive medicines, but it’s counterproductive to delay them because in the long run the insurance company ends up paying for the hospitalization and the drug rather than just the drug,” he said.

Timothy Craig, DO, of Penn State Health Allergy, Asthma, and Immunology and professor of medicine and pediatrics at Penn State College of Medicine, both in Hershey, said he was surprised at the brevity of the delays reported in Dr. Ishmael’s study. “They do much better than we do with preauthorization,” he said, noting that, in his experience, these approvals take much longer. He added that his own research has found faulty insurance plan algorithms are at the heart of these delays. “We need more studies to clarify how much this is interfering with patient care and how much risk they’re putting patients in,” he said.

The COVID-19 pandemic poses a double-edged sword for physicians managing patients with severe asthma, Dr. Craig noted. “Their asthma care is important, especially if they do test for COVID-19,” he said. On the other hand, doctors and nurses attending to COVID-19 patients will have less time to haggle with payers to expedite coverage for biologics for their severe asthma patients, he said. “I hope the flexibility is there, especially at this time to allow people to get on the biologics and stay on them,” he said.

Dr. Ishmael said these findings have serious implications because biologics are getting prescribed ever more frequently for asthma and hives. Steps his practice has taken to streamline the process include following the payer’s approval guidelines as closely as possible. This sometimes can mean making sure a patient with severe asthma has been maximized on controller medications before submitting the biologic prescription, he said. Another step is to use drug company programs to remove barriers to coverage.

Nonetheless, the approval process can be daunting even when taking those steps, he said. “Those guidelines that constitute approval may vary a lot from one insurer to another; and sometimes those guidelines are different from the criteria that studies may have used when these drugs were being evaluated in clinical trials,” he said. It would be helpful, he said, if payers used the National Heart, Lung and Blood institute and the Global Initiative for Asthma guidelines for biologics.

One of the goals of the researchers is to present their findings to payers, “to let them know, here are some of the hang-ups and the real risks associated with delaying these medications,” Dr. Ishmael said.

“When specialists especially prescribe these therapies, there’s usually a valid reason,” he said. “We really need to do something about the current process – if there are ways to make it more transparent, faster.”

Dr. Ishmael has no relevant financial relationships to disclose.

SOURCE: Ishmael F et al. AAAAI 2020. Session 3609, Presentation 558.

Patients with both type 2 diabetes and asthma who were on glucagonlike peptide receptor–1 (GLP-1R) agonists for glucose control had lower levels of a key biomarker of airway inflammation than similar patients on other types of glucose-control medications, according to results of a study to have been presented at the annual meeting of the American Academy of Asthma, Allergy, and Immunology. The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.

The findings from this study potentially replicated findings in humans that have been reported in preclinical trials.

“Our work showed that type 2 diabetics with asthma who were treated with GLP-1 receptor agonists had lower levels of periostin, and this provides really one of the first human data to show that these drugs may impact key inflammation pathways in the airway,” Dinah Foer, MD, of Brigham and Women’s Hospital, Boston, said in an interview. She described periostin as “a known critical inducer of airway mucous production and airway responsiveness.”

The study retrospectively evaluated serum samples from the Partners HealthCare Biobank of 161 adults with both asthma and type 2 diabetes, 42 of whom were on GLP-1R agonists and 119 of whom were taking non-GLP-1R agonist diabetes medications. The study used the Partners Healthcare EHR to identify eligible patients.

The study found that periostin levels were significantly decreased in GLP-1R agonist users: 19.1 ng/mL (standard deviation, +8.7) versus 27.4 ng/mL (SD, +14) in the non-GLP-1R agonist group (P = .001), Dr. Foer said. The other known mediators of asthma inflammatory pathways that were measured – interleukin-6, IL-8, sCD163, total IgE, and sST2 (soluble suppression of tumorigenesis–2) – showed no differences between the two groups, Dr. Foer said.

She said that this was the first human study to show similar results to preclinical models of asthma pathways. “What was interesting to us was that our findings were robust even when we controlled for covariates,” she added.

These findings lay the groundwork for further research into the potential therapeutic role GLP-1R agonists in asthma, Dr. Foer said. “This supports using periostin as a biomarker for novel therapeutic use of GLP-1R [agonists] in asthma,” she said. “At this point further study is needed to understand the clinical impact of GPL-1R [agonists] in asthma both for patients with type 2 diabetes and potentially in the future for patients who don’t have type 2 diabetes or metabolic disease.”

She added: “I don’t think we’re there yet; this is just one foot forward.”

The next step for researchers involves analyzing outcomes in asthmatics with type 2 diabetes on GLP-1R agonist therapy using a larger sample size as well as patients with asthma and metabolic disease, Dr. Foer said. The goal would be to identify corresponding biomarkers.

“There’s a terrific conversation in the field about the relationships between metabolism and asthma,” she said. “What our data contributes to that is, it suggests a role for metabolic pathways, specifically as it’s related GLP-1R [agonist] signaling pathways in regulating airway inflammation.”

Mark Moss, MD, associate professor of allergy & immunology at the University of Wisconsin–Madison, who was to serve as the moderator of the session, was positive about the GLP-1R agonist findings. He said in an interview: “This is promising research that provides a possible new target for the treatment of asthma.”

Dr. Foer disclosed that she has no relevant financial relationships.

SOURCE: Foer D et al. AAAAI Session 462, Abstract 784.

Patients with both type 2 diabetes and asthma who were on glucagonlike peptide receptor–1 (GLP-1R) agonists for glucose control had lower levels of a key biomarker of airway inflammation than similar patients on other types of glucose-control medications, according to results of a study to have been presented at the annual meeting of the American Academy of Asthma, Allergy, and Immunology. The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.

The findings from this study potentially replicated findings in humans that have been reported in preclinical trials.

“Our work showed that type 2 diabetics with asthma who were treated with GLP-1 receptor agonists had lower levels of periostin, and this provides really one of the first human data to show that these drugs may impact key inflammation pathways in the airway,” Dinah Foer, MD, of Brigham and Women’s Hospital, Boston, said in an interview. She described periostin as “a known critical inducer of airway mucous production and airway responsiveness.”

The study retrospectively evaluated serum samples from the Partners HealthCare Biobank of 161 adults with both asthma and type 2 diabetes, 42 of whom were on GLP-1R agonists and 119 of whom were taking non-GLP-1R agonist diabetes medications. The study used the Partners Healthcare EHR to identify eligible patients.

The study found that periostin levels were significantly decreased in GLP-1R agonist users: 19.1 ng/mL (standard deviation, +8.7) versus 27.4 ng/mL (SD, +14) in the non-GLP-1R agonist group (P = .001), Dr. Foer said. The other known mediators of asthma inflammatory pathways that were measured – interleukin-6, IL-8, sCD163, total IgE, and sST2 (soluble suppression of tumorigenesis–2) – showed no differences between the two groups, Dr. Foer said.

She said that this was the first human study to show similar results to preclinical models of asthma pathways. “What was interesting to us was that our findings were robust even when we controlled for covariates,” she added.

These findings lay the groundwork for further research into the potential therapeutic role GLP-1R agonists in asthma, Dr. Foer said. “This supports using periostin as a biomarker for novel therapeutic use of GLP-1R [agonists] in asthma,” she said. “At this point further study is needed to understand the clinical impact of GPL-1R [agonists] in asthma both for patients with type 2 diabetes and potentially in the future for patients who don’t have type 2 diabetes or metabolic disease.”

She added: “I don’t think we’re there yet; this is just one foot forward.”

The next step for researchers involves analyzing outcomes in asthmatics with type 2 diabetes on GLP-1R agonist therapy using a larger sample size as well as patients with asthma and metabolic disease, Dr. Foer said. The goal would be to identify corresponding biomarkers.

“There’s a terrific conversation in the field about the relationships between metabolism and asthma,” she said. “What our data contributes to that is, it suggests a role for metabolic pathways, specifically as it’s related GLP-1R [agonist] signaling pathways in regulating airway inflammation.”

Mark Moss, MD, associate professor of allergy & immunology at the University of Wisconsin–Madison, who was to serve as the moderator of the session, was positive about the GLP-1R agonist findings. He said in an interview: “This is promising research that provides a possible new target for the treatment of asthma.”

Dr. Foer disclosed that she has no relevant financial relationships.

SOURCE: Foer D et al. AAAAI Session 462, Abstract 784.

Patients with both type 2 diabetes and asthma who were on glucagonlike peptide receptor–1 (GLP-1R) agonists for glucose control had lower levels of a key biomarker of airway inflammation than similar patients on other types of glucose-control medications, according to results of a study to have been presented at the annual meeting of the American Academy of Asthma, Allergy, and Immunology. The AAAAI canceled their annual meeting and provided abstracts and access to presenters for press coverage.

The findings from this study potentially replicated findings in humans that have been reported in preclinical trials.

“Our work showed that type 2 diabetics with asthma who were treated with GLP-1 receptor agonists had lower levels of periostin, and this provides really one of the first human data to show that these drugs may impact key inflammation pathways in the airway,” Dinah Foer, MD, of Brigham and Women’s Hospital, Boston, said in an interview. She described periostin as “a known critical inducer of airway mucous production and airway responsiveness.”

The study retrospectively evaluated serum samples from the Partners HealthCare Biobank of 161 adults with both asthma and type 2 diabetes, 42 of whom were on GLP-1R agonists and 119 of whom were taking non-GLP-1R agonist diabetes medications. The study used the Partners Healthcare EHR to identify eligible patients.

The study found that periostin levels were significantly decreased in GLP-1R agonist users: 19.1 ng/mL (standard deviation, +8.7) versus 27.4 ng/mL (SD, +14) in the non-GLP-1R agonist group (P = .001), Dr. Foer said. The other known mediators of asthma inflammatory pathways that were measured – interleukin-6, IL-8, sCD163, total IgE, and sST2 (soluble suppression of tumorigenesis–2) – showed no differences between the two groups, Dr. Foer said.

She said that this was the first human study to show similar results to preclinical models of asthma pathways. “What was interesting to us was that our findings were robust even when we controlled for covariates,” she added.

These findings lay the groundwork for further research into the potential therapeutic role GLP-1R agonists in asthma, Dr. Foer said. “This supports using periostin as a biomarker for novel therapeutic use of GLP-1R [agonists] in asthma,” she said. “At this point further study is needed to understand the clinical impact of GPL-1R [agonists] in asthma both for patients with type 2 diabetes and potentially in the future for patients who don’t have type 2 diabetes or metabolic disease.”

She added: “I don’t think we’re there yet; this is just one foot forward.”

The next step for researchers involves analyzing outcomes in asthmatics with type 2 diabetes on GLP-1R agonist therapy using a larger sample size as well as patients with asthma and metabolic disease, Dr. Foer said. The goal would be to identify corresponding biomarkers.

“There’s a terrific conversation in the field about the relationships between metabolism and asthma,” she said. “What our data contributes to that is, it suggests a role for metabolic pathways, specifically as it’s related GLP-1R [agonist] signaling pathways in regulating airway inflammation.”

Mark Moss, MD, associate professor of allergy & immunology at the University of Wisconsin–Madison, who was to serve as the moderator of the session, was positive about the GLP-1R agonist findings. He said in an interview: “This is promising research that provides a possible new target for the treatment of asthma.”

Dr. Foer disclosed that she has no relevant financial relationships.

SOURCE: Foer D et al. AAAAI Session 462, Abstract 784.

For moderate to severe ulcerative colitis, treatment with any one of the leading biologic agents is superior to no treatment at all. And in treatment-naive patients, infliximab or vedolizumab should be used rather than adalimumab for inducing remission. These are key recommendations from the American Gastroenterological Association guideline for patients with moderate to severe ulcerative colitis (UC), published in Gastroenterology (doi: 10.1053/j.gastro.2020.01.006).

In all, the guideline comprises 11 recommendations for using immunomodulators, biologics, and small-molecule agents to induce and maintain remission in outpatients with moderate to severe UC and to decrease the need for colectomy in hospitalized patients with acute severe UC. The latest guideline follows a guideline for mild to moderate UC published last year (Gastroenterology. 2019;156[3]:748-64). A technical review accompanied the most recent publication (Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.01.007).

An updated guideline was long overdue, lead author Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center, Boston, said in an interview. “The care of patients with inflammatory bowel disease – both ulcerative colitis and Crohn’s – has become increasingly complicated with many newer drugs becoming available,” he said. “The paradigm of how we are treating the disease is evolving, but we haven’t had updated, evidence-based guidelines.” Dr. Feuerstein is the lead author of this guideline.

The guideline can also aid in influencing payers’ policies that now require step-up therapy – that is, failing with the least costly drug before moving onto newer and more effective but costlier agents – Dr. Feuerstein said. “These guidelines show now that we should be treating people based on the evidence and not based on just an insurance company’s preferred policy,” he said.

The strongest recommendation is to use the tumor necrosis factor–alpha (TNF-alpha) antagonists infliximab, adalimumab, and golimumab, the anti-integrin agent vedolizumab, or the anti-interleukin 12/23 agent ustekinumab — all biologics — or the synthetic JAK inhibitor tofacitinib rather than not treating the UC. This is the only recommendation labeled as “strong,” based on “moderate quality evidence.” The relative risk profiles the committee analyzed all favored the biologics over the JAK inhibitor.

Also based on moderate evidence is the recommendation to use infliximab or vedolizumab rather than adalimumab to induce remission in patients who had taken biologic agents before. The other recommendations are based on evidence listed at “low” or “very low” quality, or citing a “knowledge gap.”

“The quality of the evidence available is variable, and we can only make our recommendations based on the quality of the evidence there, but it doesn’t negate the effects of the guideline itself,” Dr. Feuerstein said. The strong recommendation is based on randomized clinical trials that led to the Food and Drug Administration approvals, said Aline Charabaty-Pishvaian, MD, AGAF, associate professor at Johns Hopkins University, Baltimore, and director of the Inflammatory Bowel Disease Center at Sibley Memorial Hospital, Washington. “For everything else, we do not have randomized controlled trials to help make a decision, and the recommendations are made based on the interpretation of different RCTs [randomized controlled trials], knowing that these trials have different designs, patient populations, and endpoints, as well as on experts’ opinions,” she said in an interview.

The only other recommendation based on moderate quality evidence is to use infliximab or vedolizumab rather than adalimumab to induce remission in patients who haven’t previously used biologic agents. The guideline also recommends using tofacitinib in these patients in the confines of a clinical trial; and using ustekinumab or tofacitinib rather than vedolizumab or adalimumab in patients who’ve already been on infliximab, particularly if they haven’t responded to treatment.

The guideline also recommends against thiopurine monotherapy to induce remission, but, for maintenance of remission, recommends such treatment vs. none. However, the guideline suggests against methotrexate monotherapy to induce or maintain remission. And biologic monotherapy is preferred to thiopurine to induce remission, but the guideline makes no recommendation for biologic vs. thiopurine monotherapy to maintain remission. Likewise, combining vedolizumab or ustekinumab with thiopurines or methotrexate is preferred to monotherapy with either a biologic or thiopurine.

The guideline also addresses step-up therapy. It suggests biologics as a first treatment, either as monotherapy or in combination with an immunomodulator, rather than a step-up after failure with 5-aminosalicylates. Also, it recommends against continuing 5-aminosalicylates to induce or maintain remission after a patient has achieved remission with biologics as monotherapy or in combination with immunomodulators or tofacitinib.

The guideline also offers four recommendations for hospitalized patients with acute severe ulcerative colitis: use of intravenous 40-60 mg/d methylprednisolone rather than higher dose IV corticosteroids, no adjunctive antibiotics in the absence of infection; use of infliximab or cyclosporine when IV corticosteroids fail, and no recommendation on the use of intensive vs. standard infliximab dosing when IV corticosteroids fail and the patient is already on infliximab.

The guideline will be meaningful in closing the evidence gap going forward because it can help direct the design of clinical trials, Dr. Charabaty-Pishvaian said. “The guideline highlights areas of need in terms of randomized clinical trials,” she said. “We need these trials to answer the questions we ask ourselves in our daily practice when managing patients with UC: Which drug to choose as the first-line agent? Which drug is the second-line therapy when the disease doesn’t respond or loses response to the first-line agent? Do we need to use combination therapy with all biologics, or only with anti-TNF-alpha agents? For how long? Can we use vedolizumab or ustekinumab as monotherapy when used as a first-line agent? And is there any advantage in adding an immunomodulator when these agents are used as third- or fourth-line therapy?”

Dr. Feuerstein has no relevant financial relationships to disclose. Guideline author Kim Isaacs, MD, disclosed relationships with AbbVie, Takeda, UCB, Janssen and Hoffmann-Laroche. All other committee members have no relevant disclosures.

*This story was updated on 5/7/2020.

SOURCE: Feuerstein JD et al. on behalf of the AGA Institute Clinical Guidelines Committee. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.01.006.

For moderate to severe ulcerative colitis, treatment with any one of the leading biologic agents is superior to no treatment at all. And in treatment-naive patients, infliximab or vedolizumab should be used rather than adalimumab for inducing remission. These are key recommendations from the American Gastroenterological Association guideline for patients with moderate to severe ulcerative colitis (UC), published in Gastroenterology (doi: 10.1053/j.gastro.2020.01.006).

In all, the guideline comprises 11 recommendations for using immunomodulators, biologics, and small-molecule agents to induce and maintain remission in outpatients with moderate to severe UC and to decrease the need for colectomy in hospitalized patients with acute severe UC. The latest guideline follows a guideline for mild to moderate UC published last year (Gastroenterology. 2019;156[3]:748-64). A technical review accompanied the most recent publication (Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.01.007).

An updated guideline was long overdue, lead author Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center, Boston, said in an interview. “The care of patients with inflammatory bowel disease – both ulcerative colitis and Crohn’s – has become increasingly complicated with many newer drugs becoming available,” he said. “The paradigm of how we are treating the disease is evolving, but we haven’t had updated, evidence-based guidelines.” Dr. Feuerstein is the lead author of this guideline.

The guideline can also aid in influencing payers’ policies that now require step-up therapy – that is, failing with the least costly drug before moving onto newer and more effective but costlier agents – Dr. Feuerstein said. “These guidelines show now that we should be treating people based on the evidence and not based on just an insurance company’s preferred policy,” he said.

The strongest recommendation is to use the tumor necrosis factor–alpha (TNF-alpha) antagonists infliximab, adalimumab, and golimumab, the anti-integrin agent vedolizumab, or the anti-interleukin 12/23 agent ustekinumab — all biologics — or the synthetic JAK inhibitor tofacitinib rather than not treating the UC. This is the only recommendation labeled as “strong,” based on “moderate quality evidence.” The relative risk profiles the committee analyzed all favored the biologics over the JAK inhibitor.

Also based on moderate evidence is the recommendation to use infliximab or vedolizumab rather than adalimumab to induce remission in patients who had taken biologic agents before. The other recommendations are based on evidence listed at “low” or “very low” quality, or citing a “knowledge gap.”

“The quality of the evidence available is variable, and we can only make our recommendations based on the quality of the evidence there, but it doesn’t negate the effects of the guideline itself,” Dr. Feuerstein said. The strong recommendation is based on randomized clinical trials that led to the Food and Drug Administration approvals, said Aline Charabaty-Pishvaian, MD, AGAF, associate professor at Johns Hopkins University, Baltimore, and director of the Inflammatory Bowel Disease Center at Sibley Memorial Hospital, Washington. “For everything else, we do not have randomized controlled trials to help make a decision, and the recommendations are made based on the interpretation of different RCTs [randomized controlled trials], knowing that these trials have different designs, patient populations, and endpoints, as well as on experts’ opinions,” she said in an interview.

The only other recommendation based on moderate quality evidence is to use infliximab or vedolizumab rather than adalimumab to induce remission in patients who haven’t previously used biologic agents. The guideline also recommends using tofacitinib in these patients in the confines of a clinical trial; and using ustekinumab or tofacitinib rather than vedolizumab or adalimumab in patients who’ve already been on infliximab, particularly if they haven’t responded to treatment.

The guideline also recommends against thiopurine monotherapy to induce remission, but, for maintenance of remission, recommends such treatment vs. none. However, the guideline suggests against methotrexate monotherapy to induce or maintain remission. And biologic monotherapy is preferred to thiopurine to induce remission, but the guideline makes no recommendation for biologic vs. thiopurine monotherapy to maintain remission. Likewise, combining vedolizumab or ustekinumab with thiopurines or methotrexate is preferred to monotherapy with either a biologic or thiopurine.

The guideline also addresses step-up therapy. It suggests biologics as a first treatment, either as monotherapy or in combination with an immunomodulator, rather than a step-up after failure with 5-aminosalicylates. Also, it recommends against continuing 5-aminosalicylates to induce or maintain remission after a patient has achieved remission with biologics as monotherapy or in combination with immunomodulators or tofacitinib.

The guideline also offers four recommendations for hospitalized patients with acute severe ulcerative colitis: use of intravenous 40-60 mg/d methylprednisolone rather than higher dose IV corticosteroids, no adjunctive antibiotics in the absence of infection; use of infliximab or cyclosporine when IV corticosteroids fail, and no recommendation on the use of intensive vs. standard infliximab dosing when IV corticosteroids fail and the patient is already on infliximab.

The guideline will be meaningful in closing the evidence gap going forward because it can help direct the design of clinical trials, Dr. Charabaty-Pishvaian said. “The guideline highlights areas of need in terms of randomized clinical trials,” she said. “We need these trials to answer the questions we ask ourselves in our daily practice when managing patients with UC: Which drug to choose as the first-line agent? Which drug is the second-line therapy when the disease doesn’t respond or loses response to the first-line agent? Do we need to use combination therapy with all biologics, or only with anti-TNF-alpha agents? For how long? Can we use vedolizumab or ustekinumab as monotherapy when used as a first-line agent? And is there any advantage in adding an immunomodulator when these agents are used as third- or fourth-line therapy?”

Dr. Feuerstein has no relevant financial relationships to disclose. Guideline author Kim Isaacs, MD, disclosed relationships with AbbVie, Takeda, UCB, Janssen and Hoffmann-Laroche. All other committee members have no relevant disclosures.

*This story was updated on 5/7/2020.

SOURCE: Feuerstein JD et al. on behalf of the AGA Institute Clinical Guidelines Committee. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.01.006.

For moderate to severe ulcerative colitis, treatment with any one of the leading biologic agents is superior to no treatment at all. And in treatment-naive patients, infliximab or vedolizumab should be used rather than adalimumab for inducing remission. These are key recommendations from the American Gastroenterological Association guideline for patients with moderate to severe ulcerative colitis (UC), published in Gastroenterology (doi: 10.1053/j.gastro.2020.01.006).

In all, the guideline comprises 11 recommendations for using immunomodulators, biologics, and small-molecule agents to induce and maintain remission in outpatients with moderate to severe UC and to decrease the need for colectomy in hospitalized patients with acute severe UC. The latest guideline follows a guideline for mild to moderate UC published last year (Gastroenterology. 2019;156[3]:748-64). A technical review accompanied the most recent publication (Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.01.007).

An updated guideline was long overdue, lead author Joseph D. Feuerstein, MD, of Beth Israel Deaconess Medical Center, Boston, said in an interview. “The care of patients with inflammatory bowel disease – both ulcerative colitis and Crohn’s – has become increasingly complicated with many newer drugs becoming available,” he said. “The paradigm of how we are treating the disease is evolving, but we haven’t had updated, evidence-based guidelines.” Dr. Feuerstein is the lead author of this guideline.

The guideline can also aid in influencing payers’ policies that now require step-up therapy – that is, failing with the least costly drug before moving onto newer and more effective but costlier agents – Dr. Feuerstein said. “These guidelines show now that we should be treating people based on the evidence and not based on just an insurance company’s preferred policy,” he said.

The strongest recommendation is to use the tumor necrosis factor–alpha (TNF-alpha) antagonists infliximab, adalimumab, and golimumab, the anti-integrin agent vedolizumab, or the anti-interleukin 12/23 agent ustekinumab — all biologics — or the synthetic JAK inhibitor tofacitinib rather than not treating the UC. This is the only recommendation labeled as “strong,” based on “moderate quality evidence.” The relative risk profiles the committee analyzed all favored the biologics over the JAK inhibitor.

Also based on moderate evidence is the recommendation to use infliximab or vedolizumab rather than adalimumab to induce remission in patients who had taken biologic agents before. The other recommendations are based on evidence listed at “low” or “very low” quality, or citing a “knowledge gap.”

“The quality of the evidence available is variable, and we can only make our recommendations based on the quality of the evidence there, but it doesn’t negate the effects of the guideline itself,” Dr. Feuerstein said. The strong recommendation is based on randomized clinical trials that led to the Food and Drug Administration approvals, said Aline Charabaty-Pishvaian, MD, AGAF, associate professor at Johns Hopkins University, Baltimore, and director of the Inflammatory Bowel Disease Center at Sibley Memorial Hospital, Washington. “For everything else, we do not have randomized controlled trials to help make a decision, and the recommendations are made based on the interpretation of different RCTs [randomized controlled trials], knowing that these trials have different designs, patient populations, and endpoints, as well as on experts’ opinions,” she said in an interview.

The only other recommendation based on moderate quality evidence is to use infliximab or vedolizumab rather than adalimumab to induce remission in patients who haven’t previously used biologic agents. The guideline also recommends using tofacitinib in these patients in the confines of a clinical trial; and using ustekinumab or tofacitinib rather than vedolizumab or adalimumab in patients who’ve already been on infliximab, particularly if they haven’t responded to treatment.

The guideline also recommends against thiopurine monotherapy to induce remission, but, for maintenance of remission, recommends such treatment vs. none. However, the guideline suggests against methotrexate monotherapy to induce or maintain remission. And biologic monotherapy is preferred to thiopurine to induce remission, but the guideline makes no recommendation for biologic vs. thiopurine monotherapy to maintain remission. Likewise, combining vedolizumab or ustekinumab with thiopurines or methotrexate is preferred to monotherapy with either a biologic or thiopurine.

The guideline also addresses step-up therapy. It suggests biologics as a first treatment, either as monotherapy or in combination with an immunomodulator, rather than a step-up after failure with 5-aminosalicylates. Also, it recommends against continuing 5-aminosalicylates to induce or maintain remission after a patient has achieved remission with biologics as monotherapy or in combination with immunomodulators or tofacitinib.

The guideline also offers four recommendations for hospitalized patients with acute severe ulcerative colitis: use of intravenous 40-60 mg/d methylprednisolone rather than higher dose IV corticosteroids, no adjunctive antibiotics in the absence of infection; use of infliximab or cyclosporine when IV corticosteroids fail, and no recommendation on the use of intensive vs. standard infliximab dosing when IV corticosteroids fail and the patient is already on infliximab.

The guideline will be meaningful in closing the evidence gap going forward because it can help direct the design of clinical trials, Dr. Charabaty-Pishvaian said. “The guideline highlights areas of need in terms of randomized clinical trials,” she said. “We need these trials to answer the questions we ask ourselves in our daily practice when managing patients with UC: Which drug to choose as the first-line agent? Which drug is the second-line therapy when the disease doesn’t respond or loses response to the first-line agent? Do we need to use combination therapy with all biologics, or only with anti-TNF-alpha agents? For how long? Can we use vedolizumab or ustekinumab as monotherapy when used as a first-line agent? And is there any advantage in adding an immunomodulator when these agents are used as third- or fourth-line therapy?”

Dr. Feuerstein has no relevant financial relationships to disclose. Guideline author Kim Isaacs, MD, disclosed relationships with AbbVie, Takeda, UCB, Janssen and Hoffmann-Laroche. All other committee members have no relevant disclosures.

*This story was updated on 5/7/2020.

SOURCE: Feuerstein JD et al. on behalf of the AGA Institute Clinical Guidelines Committee. Gastroenterology. 2020. doi: 10.1053/j.gastro.2020.01.006.